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ANO31905 in Combination With Chemotherapy for CLDN18.2-Positive Locally Advanced Unresectable or Metastatic Pancreatic Cancer
ANO31905, a CLDN18.2-targeted agent, is being studied in combination with chemotherapy (AG or mFOLFIRINOX) as first-line treatment for CLDN18.2-positive locally advanced unresectable or metastatic pancreatic adenocarcinoma.
NCT07444541 · Phase 1/2 · Anova Innovation Limited
Recruiting sites: California, Florida, Texas
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Inclusion Criteria:
1. Patients voluntarily participate in the study and sign the written ICF;
2. Males or females aged ≥ 18 at the time of signing the ICF;
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
4. Expected survival ≥ 3 months;
5. Histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma (including adenosquamous cell carcinoma) which is locally advanced unresectable or metastatic with the first diagnosis within 3 months before the first dose (clinical staging criteria are based on AJCC 8th edition);
6. Those who have not received any anti-tumor treatment for locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma, including but not limited to surgery, radiotherapy, and chemotherapy; however, if they have received palliative radiotherapy for metastases to bone and/or pain ≥14 days before the first dose of the study treatment and have recovered from all acute toxicities, they can be included. For previous systemic therapy in the neoadjuvant and/or adjuvant stage, the time of disease recurrence or progression must be ≥ 6 months after the last dose and within 3 months before the first study dose;
7. At least one measurable lesion according to RECIST v1.1;
8. Tumor tissue samples are determined to be CLDN18.2-positive by immunohistochemistry (IHC) in the central laboratory, defined as ≥1% of tumor cells with membranous staining intensity ≥1+ determined by IHC;
9. Patients with sufficient organ function within 7 days before the first study dose;
10. Non-pregnant or -lactating women; patients of childbearing potential (male and female) must agree to use a reliable method of contraception with their partner from the signing of the ICF until at least 3 months for Cohort A or 6 months for Cohort B (for males) or 6 months for Cohort A or 9 months for Cohort B (for females) after the last dose; female patients of childbearing age must have a negative serum pregnancy test within 7 days before the first study dose.
Exclusion Criteria:
1. Patients with other malignant tumors except pancreatic adenocarcinoma within 5 years before the first dose of the study treatment (except for in situ cancer of the cervix, basal cell or squamous epithelial cell skin cancer, localized prostate cancer, or ductal carcinoma in situ of the breast);
2. Patients who have previously received an organ transplant/allogeneic bone marrow transplant or are awaiting an organ transplant/allogeneic bone marrow transplant during the expected study period;
3. Patients who have received treatment with herbal medicines with well documented anti-tumor effects or indications within 14 days before the first study dose;
4. Patients who have participated in other interventional clinical trials and used interventional measures (such as drugs or devices) within 28 days before the first study dose;
5. Patients who have undergone major organ surgery (excluding aspiration biopsy and venous catheterization) or experienced significant trauma within 28 days before the first study dose;
6. Patients who have received attenuated live vaccines within 28 days before the first study dose or are expected to receive attenuated live vaccines during study treatment;
7. Patients with toxic reactions to previous anti-tumor therapy which haven't recovered to Grade ≤ 1 according to NCI-CTCAE v6.0 criteria (for CRS and ICANS, Grade ≤ 1 as per the ASTCT)),) excluding alopecia (any grade) or other toxic reactions with no safety risk considered by the investigator;
8. Patients who have previously received treatment targeting CLDN18.2, including but not limited to monoclonal antibodies, bispecific antibodies, chimeric antigen receptor T-cell immunotherapy (CAR-T), or antibody-drug conjugate (ADC);
9. Patients who have received corticosteroids for systemic use (\> 10 mg/day prednisone or equivalent) or other immunosuppressants (including but not limited to cyclophosphamide, methotrexate, and thalidomide) within 14 days before the first study dose or expected to receive during study treatment, except that substitution therapy with physiological doses of corticosteroids (ie, ≤ 10 mg/day prednisone or equivalent) is allowed for insufficiency adrenal cortex in the absence of active autoimmune disorders, topical, ocular, intra-articular, intranasal and inhalation use of glucocorticoids are allowed, and the use of glucocorticoids to prevent contrast media allergy is allowed;
10. Patients with a history of active autoimmune disorders or autoimmune disorders requiring systemic treatment;
11. Patients who have previously experienced serious adverse reactions related to immunotherapy, or intolerance to immunotherapy;
12. Patients with known hypersensitivity to any component or excipient of ANO31905, gemcitabine, and nanoparticle albumin-bound paclitaxel;
13. For Cohort B, use of strong inhibitors or inducers of CYP3A or use of strong inhibitors of UGT1A1.
14. For Cohort B, known low or absent dihydropyrimidine dehydrogenase (DPD) activity. Where required by local regulations, testing for DPD deficiency must be performed using a validated method which is recommended by local health authorities.
15. Patients with known metastases to the central nervous system;
16. Patients with a poor nutrition condition of indicated by a weight ≤40 kg or body mass index (BMI) \<18.0 kg/m2; if symptomatic nutritional support is provided and the condition is corrected before the first study dose, continued screening for enrollment may be considered after assessment by the investigator;
17. Patients a with serious systemic infection or a medically unexplained fever ≥ 38.5°C (101.3°F) within 28 days before the first study dose;
18. Patients with severe cardiovascular and cardiovascular diseases;
19. Presence risks of thrombosis or bleeding:
20. Patients having severe advanced diseases with comorbidities that may be life-threatening in the short term;
21. Patients with gastrointestinal diseases that are not suitable for enrollment as judged by the investigator;
22. Patients with known or suspected interstitial pneumonitis, moderate to severe lung diseases that seriously affect respiratory function
23. Patients with hepatitis B, hepatitis C, or a known HIV positive history or positive HIV screening;
24. Patients with other conditions that may place the patients at increased undue study-related risks.
BRain-AVOidant Proton Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumor Malignancies
This trial evaluates brain-avoidant proton craniospinal irradiation (BRAVO-pCSI) as treatment for leptomeningeal metastases arising from breast cancer, NSCLC, or other solid tumors.
NCT07789912 · Phase N/A · University of Miami
Recruiting sites: Florida
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Inclusion Criteria:
1. Participants with leptomeningeal metastases established radiographically and/or through Cerebrospinal Fluid (CSF) cytology or circulating tumor cells (CTCs). Participants may have newly diagnosed or recurrent LM.
2. Pathologically confirmed breast or non-small cell lung cancer (NSCLC) primary (group 1 and). Pathologically confirmed solid tumor malignancy (group 2).
3. Participants with adequate bone marrow function.
4. Participants with a Karnofsky Performance Status (KPS) ≥ 60.
5. Male and female participants ages ≥ 18 years.
6. Female participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method.
7. Male participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method.
Exclusion Criteria:
1. Participants with metastases within the memory-avoidance structures (hippocampus, corpus callosum, fornix, amygdala) that preclude developing a treatment plan that respects dosimetric constraints for these structures.
2. Participants with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy.
3. Participants with extensive systemic disease and without reasonable systemic treatment options.
4. Participants unable to undergo MRI brain and spine with gadolinium contrast.
5. Participants who have had radiation therapy to the spinal cord with equivalent dose in 2Gy fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using α/β of 3.
6. Female participants who are pregnant or lactating.
7. Participants with impaired decision-making capacity.
Phase 1 Study of STRO-006 in Adults With Refractory Solid Tumors That Are Recurrent or Metastatic
STRO-006, an ITGB6-targeted antibody-drug conjugate, is being studied as monotherapy or combined with the PD-1 inhibitor pembrolizumab in a first-in-human dose-escalation/expansion trial for patients with refractory, recurrent or metastatic solid tumors including HNSCC, NSCLC, esophageal/gastric, colorectal, endometrial, urothelial, and breast cancers.
NCT07807345 · Phase 1 · Sutro Biopharma, Inc.
Recruiting sites: Florida, Massachusetts, Oklahoma, Texas, Virginia
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Inclusion Criteria:
* Histologically or cytologically documented refractory solid tumors that are recurrent or metastatic including: HNSCC (excluding EBV-positive nasopharyngeal carcinoma), NSCLC, esophageal/gastric cancer, colorectal cancer, endometrial carcinoma, urothelial carcinoma, and breast cancer (HR-positive \[HER2-positive or HER2-negative\] and TNBC subtype)
* Age ≥ 18 years
* Life expectancy of at least 3 months
* Willingness and ability to comply with the study protocol and long
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1-term follow-up (LTFU) assessments
* Has received standard systemic therapies with known clinical benefit, or is considered inappropriate for such therapies, in the opinion of the investigator. In the dose escalation Phases (Parts 1A and 1C), there is no limit on the number of prior therapies
* Expansion Phase (Part 1B) only: Up to two prior therapies are allowed. For participants with AGA-driven adenocarcinoma NSCLC up to four prior therapies are allowed
* Measurable disease per RECIST v1.1.
* Adequate hematologic and organ function
Exclusion Criteria:
* Prior anticancer treatment with an ADC with a TOP1 inhibitor payload. (Prior therapy with an ITGB6-targeted ADC is otherwise allowed.)
* Prior anticancer therapy (prior to first dose of study treatment): chemotherapy within ≤ 2 weeks, ICI ≤ 3 weeks, ADCs ≤ 3 weeks, palliative radiation therapy ≤ 2 weeks, and major surgery ≤ 4 weeks of C1D1. If not specified, ≥ 5 half-lives or 2 weeks, whichever is longer, since administration of prior therapy must have elapsed
* Residual Common Terminology Criteria for Adverse Events (CTCAE) v5 ≥ Grade 2 toxicity from prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 peripheral neuropathy, which is controlled, and endocrinopathies secondary to prior ICI controlled by hormonal treatment. For Part 1C only: discontinued prior immunotherapy due to treatment-related toxicity
* Untreated or active brain metastases and/or leptomeningeal disease
* Participants with active ILD or active, non-infectious pneumonitis or a history of active pneumonitis ≤ 6 months from the first dose of study treatment
* Significant, concurrent renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease that could impact participation in this clinical trial
* Previous solid organ or bone marrow transplantation
* Concurrent participation in another therapeutic treatment trial
Single FrAction Interstitial BreaSt BracHytherApy
Single-fraction (16 Gy) multicatheter interstitial accelerated partial breast irradiation is studied as adjuvant radiotherapy after lumpectomy in early-stage DCIS/invasive breast cancer patients with negative margins.
NCT07654257 · Phase 2 · Virginia Commonwealth University
Recruiting sites: Virginia
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Inclusion Criteria:
* Female
* New diagnosis of Ductal Carcinoma in Situ (DCIS) and/or invasive breast carcinoma per histologic evaluation
* Age 40-85 at diagnosis
* Previous lumpectomy with surgical margins histologically free of invasive tumor and DCIS as determined by the pathologist
* T stage of Tis, T1, or T2
* T2 tumors must be ≤3 cm in maximum diameter
* If the tumor is human epidermal growth factor receptor (HER2)-positive, the patient is planning to receive or has already received HER2-directed therapy
* For patients with invasive breast cancer, an axillary staging procedure must be performed (either sentinel node biopsy alone or axillary dissection \[with a minimum of 6 axillary nodes removed\]) and the axillary node(s) must be pathologically negative Note: N0(i+) is not an exclusion criterion
Note: Patients meeting all of the following criteria are not required to undergo the axillary staging procedure:
* ≥70 years of age
* Estrogen receptor (ER)+, progesterone receptor (PR)+/-, HER2-
* Grade 1-2 breast cancer
* Tumor ≤2 cm in size
Note: If patients meet all the following criteria, the decision to avoid sentinel lymph node biopsy can be at the discretion of the breast surgeon:
* 50-69 years of age
* Grade 1-2 breast cancer
* Clinically negative axilla by ultrasound and/or magnetic resonance imaging (MRI)
* ER+, PR+, HER2-
* Tumor ≤2 cm in size
* Agrees to comply with aromatase inhibitor recommendation
* Ability to begin brachytherapy within 12 weeks following lumpectomy, re- excision of margins, or completion of chemotherapy
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Pregnant or breastfeeding
* Active collagen-vascular disease
* Paget's disease of the breast
* Any prior history of DCIS or invasive breast cancer prior to the current diagnosis
* Any prior history of breast radiation therapy (RT) or thoracic RT for any condition
* Multicentric carcinoma (DCIS or invasive)
* Synchronous bilateral invasive or non-invasive breast cancer
* Surgical margins that cannot be microscopically assessed or that are positive
* Treatment with neoadjuvant chemotherapy
* Excision cavity that cannot be clearly delineated or is not amenable to implant per the treating investigator
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
A Phase I/II, First-in-Human Study to Evaluate TJ102 in Participants With Advanced or Metastatic Ovarian Cancer and Other Solid Tumors.
TJ102 is a CDH6/FRα-directed antibody-drug conjugate with dual payloads, studied in advanced or metastatic ovarian cancer and other solid tumors that have progressed on standard therapies.
NCT07778498 · Phase 1/2 · Phrontline Biopharma
Recruiting sites: California, Florida, New York, Pennsylvania, Tennessee, Texas, Virginia
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Main Inclusion Criteria:
1. Has histologically or cytologically documented locally advanced or metastatic high-grade serous epithelial ovarian cancer, including ovarian, fallopian tube, or primary peritoneal carcinoma, that is not amenable to curative surgery or radiotherapy, and has demonstrated radiographic disease progression on the most recent line of systemic therapy.
2. Prior exposure to a platinum-containing regimen is mandatory. Platinum-resistant disease is defined as disease progression during or within 6 months following completion of the most recent platinum-containing regimen. Patients with platinum-sensitive disease may be eligible during Phase 1 if they have received at least 2 prior lines of platinum-containing systemic therapy.
3. Prior Lines of therapy:
Subjects must have received at least one (≥1) and no more than four (≤4) prior lines of systemic therapy in the advanced or metastatic setting and have progressed on, been intolerant to, or be ineligible for standard therapies available in their local region. Prior treatment with mirvetuximab soravtansine and/or bevacizumab is permitted but not required, reflecting regional differences in standard of care, regulatory approval status, availability, or access.
Hormonal therapy and maintenance therapy, including PARP inhibitors or bevacizumab maintenance, are not counted as prior lines of systemic therapy unless administered for treatment of progressive disease.
4. Have at least one measurable lesion by RECIST v1.1 (Eisenhauer et al., 2009) for solid tumors;
5. ≥18 years old;
6. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) of 0 to 1;
7. Life expectancy of ≥12 weeks;
8. Patients with adequate organ function and the laboratory test criteria specifically defined as follows within 7 days prior to the first dosing;
Main Exclusion Criteria:
1. Has know hypersensitivity to any component of TJ102 or has a history of severe hypersensitivity reactions to other monoclonal antibodies.
2. Has received more than two (2) prior antibody-drug conjugate (ADC) therapies in the advanced or metastatic disease setting, including ADCs containing topoisomerase I inhibitor payloads (e.g., SN-38, DXd, exatecan derivatives) or antimicrotubule payloads (e.g., MMAE, DM1/DM4, auristatins, maytansinoids).
3. Prior therapy with any antibody-drug conjugate (ADC) whose cytotoxic payload is eribulin or a structural derivative thereof is prohibited in the advanced/metastatic disease setting.
4. Has received mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks prior to the first administration; Has received other chemotherapy, biological therapy, major surgery, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase) and other anti-tumor therapy within 5 half-lives or 28 days, whichever is shorter, prior to the first administration of TJ102; Has received anti-tumor herbal medicine within 14 days prior to first dose of TJ102;
5. Has received a strong or moderate CYP3A4 inhibitor within 3 half-lives prior to first dose of TJ102;
6. Received an investigational drug within 28 days or 2 half-lives (whichever is shorter) prior to first dose of TJ102; Current participation in other interventional clinical studies (participation in survival follow-up is allowed);
7. Toxic effects of prior anti-tumor therapy have not recovered to NCI-CTCAE V6.0 Grade ≤1 (excluding alopecia and skin pigmentation). Subject with irreversible toxicities caused by prior anti-tumor therapy (eg, hearing loss) that will not increase the safety risk may be eligible per the discretion of the Investigator;
8. Has a history of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis can't be ruled out by imaging at screening;
9. Presence of severe dry eye syndrome, severe keratitis, severe conjunctivitis, or other severe conditions that may increase the risk of corneal epithelial damage at the discretion of investigator;
10. Presence of Grade ≥2 or history of Grade ≥3 peripheral neuropathy.
11. Uncontrolled or significant cardiovascular disease
12. For patients with documented positive virology status, as confirmed by Screening hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) tests, only the following patients may be eligible as evaluated by the sponsor and investigator:
Patients with active hepatitis B: HBV DNA ≤500 IU/mL during Screening. Patients who are hepatitis C virus antibody positive (HCV Ab+), should have controlled infection (HCV RNA≤ULN by polymerase chain reaction \[PCR\] either spontaneously or in response to a successful prior course of anti-HCV therapy at Screening). Patients with controlled infections must undergo periodic monitoring of HCV RNA as per treating physician.
13. Severe infection, including but not limited to hospitalization due to infection, bacteraemia, or severe pneumonia complications, occurs within 4 weeks prior to initiation of study treatment; Or patients who received therapeutic oral or intravenous antibiotics and who received prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease) within two weeks prior to starting study treatment.
14. Active central nervous system (CNS) metastases or meningeal metastases. Subjects may be enrolled in the study if their CNS metastases have received adequate local therapy and have been clinical stable for at least 4 weeks (i.e., imaging shows no progression of the brain lesion and neurologically relevant symptoms are stable), and require a dose of prednisone of ≤20 mg/day (or equivalent dose). Subjects with untreated CNS metastases are excluded.
15. Other malignancies within 3 years prior to initiation of study treatment (Note: does not include tumors with a negligible risk for metastasis or death, eg, non-melanoma basal cell carcinoma or squamous cell carcinoma of the skin, breast/cervical carcinoma in situ, superficial bladder carcinoma that have received radical treatment and without evidence of disease recurrence);
16. Female patients who are lactating or breastfeeding;
17. The investigator believes that the subject may have other factors that may affect the results of the study and interfere with the subject's participation in the entire study process, including previous or existing physical conditions, abnormal treatment or laboratory tests, and the subject's unwillingness to comply with all procedures, restrictions, and requirements of the study.
A Study Evaluating the Safety of Inavolisib and Fulvestrant With or Without Palbociclib in Participants With Advanced Breast Cancer (ABC) and Type 2 Diabetes
Inavolisib, an oral PI3Kα inhibitor, is studied in combination with fulvestrant (with or without the CDK4/6 inhibitor palbociclib) in participants with PIK3CA-mutated, HR+/HER2-negative advanced breast cancer and type 2 diabetes who have not received prior systemic therapy for advanced/metastatic disease.
NCT07748208 · Phase 2 · Hoffmann-La Roche
Recruiting sites: District of Columbia, Georgia, Nebraska, New York, West Virginia
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Inclusion Criteria:
* Type 2 diabetes with laboratory fasting blood glucose \< 185 milligrams per deciliter (mg/dL) and HbA1c \<= 8% on any stable anti-hyperglycemic regimen excluding insulin short-term insulin dosing
* Eligible for triplet of inavolisib, fulvestrant and palbociclib: no prior systemic therapy for locally advanced unresectable or metastatic disease
* Confirmed diagnosis of HR+/HER2- breast cancer
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
Exclusion Criteria:
* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
* Metaplastic breast cancer
* Any history of Type 1 diabetes
* Severe hyper- or hypoglycemia event within 6 months of initiation of study treatment
* Any history of leptomeningeal disease or carcinomatous meningitis
* Known and untreated, or active central nervous system (CNS) metastases Participants with a history of treated CNS metastases are eligible
* Active inflammatory or conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
* Symptomatic active lung disease
* History of active bowel inflammation or active inflammatory bowel disease
A Study of [225Ac]Ac-AKY-2519 in Patients With B7-H3 Expressing Solid Tumors
[225Ac]Ac-AKY-2519, a B7-H3-targeted radiopharmaceutical (alpha-emitter) therapy, is being studied in a Phase 1 trial for B7-H3-expressing advanced/metastatic NSCLC, SCLC, HNSCC, esophageal squamous cell carcinoma, colorectal cancer, and metastatic castration-resistant prostate cancer.
NCT07887971 · Phase 1 · Aktis Oncology, Inc.
Recruiting sites: Florida
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Inclusion Criteria:
* Age ≥ 18 years
* Histologic or cytologic confirmation of locally advanced or metastatic NSCLC, ES-SCLC, HNSCC, ESCC, CRC or prostatic adenocarcinoma
* Radiologic confirmation on CT of at least one measurable tumor lesion per RECIST v1.1
* ECOG Performance Status of 0 or 1
* Adequate end-organ function
* Ability to give informed consent and comply with study requirements
* Patients with CNS metastases are eligible if they have received therapy and are neurologically stable, asymptomatic and not receiving corticosteroids
Exclusion Criteria:
* Prior treatment with a B7-H3 targeted therapy
* Prior treatment with a targeted radiotherapy
* Received an investigational agent within the previous 28 days
* Prior treatment with a cytotoxic chemotherapy, targeted therapy, biologic agent, immunotherapy or external-beam radiotherapy within the previous 28 days
* Impaired cardiac function or clinically significant cardiac disease
* Concurrent serious medical condition that would impair study participation or impact the assessment of treatment related toxicity
A Study to Assess Intravenous ABBV-1480 Combined With Chemotherapy Versus Pembrolizumab Combined With Chemotherapy for the First Line Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer in Adult Participants
ABBV-1480, an investigational agent whose mechanism is not stated in the registry, is being studied in combination with platinum-based chemotherapy versus pembrolizumab plus chemotherapy as first-line treatment for locally advanced or metastatic squamous non-small cell lung cancer.
NCT07756645 · Phase 3 · AbbVie
Recruiting sites: Indiana
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Inclusion Criteria:
* Adult subjects with a histologically or cytologically confirmed diagnosis of Stage IIIB, IIIC, or IV sqNSCLC that is not amenable to curative treatment
* At least one lesion with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by the local site investigator/radiology assessment.
* Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate hematological, renal, hepatic, and coagulation function.
* Females of childbearing potential must have a negative pregnancy test
Exclusion Criteria:
* Prior systemic treatment received for locally advanced or metastatic NSCLC.
* Histologically or cytologically confirmed non-sqNSCLC.
* Known actionable genomic alterations (including EGFR, ALK, ROS1, BRAF, NTRK, RET, and MET) for which first-line approved therapies are available.
* Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
A Trial to Evaluate Safety, Tolerability, and Preliminary Efficacy of Misetionamide (GP-2250) as Monotherapy or in Combination With Gemcitabine
Misetionamide (GP-2250), an oxathiazine-based agent that induces ROS-mediated apoptosis in tumor cells, is being evaluated as monotherapy in a phase 1 dose-escalation trial for platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.
NCT03854110 · Phase 1 · Persevere Therapeutics Inc.
Recruiting sites: Illinois, Kansas, Massachusetts, Pennsylvania
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Abridged Inclusion Criteria:
1. Capable of giving signed informed consent: Regulatory, Ethical, and Trial Oversight Considerations which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Subjects age \> 18 years at the time of trial entry.
3. Pathologically proven platinum-resistant epithelial ovarian, fallopian, or primary peritoneal cancer, with high-grade serous ovarian carcinoma (HGSOC) or a predominantly serous/endometroid component. Platinum-resistant disease, defined as disease progression within 6 months of last dose of platinum-based chemotherapy.
4. Maximum of 2 prior regimens for platinum-resistant disease. Subjects who are positive for high FR alpha (defined per the FDA approved companion diagnostic test (ELAHERE prescribing information) must have received MIRV. Candidates for MIRV with contraindications or documented intolerance are eligible pending documentation of discussion with the Medical Monitor.
5. CT/MRI evidence of measurable disease per RECIST Version 1.1 defined as at least one lesion not previously irradiated that can be measured at baseline as 10 mm in the longest diameter (except lymph nodes which must have a short axis of 15 mm). Tumor lesions in previously irradiated area or in area subject to other loco-regional therapy are usually not considered measurable unless progression has been demonstrated in the lesion. Lesions selected as targets for response assessment should not be biopsied.
6. ECOG performance status of 0-1
7. Subjects with known central nervous system metastasis must have undergone brain targeted treatment and must be asymptomatic or radiographically and clinically stable (including not requiring steroids or anti-seizure medications) for at least 4 weeks prior to enrollment.
8. Subjects must have adequate organ function as indicated by the following laboratory values:
1. Absolute neutrophil count (ANC) ≥ 1,500 /mL
2. Platelets ≥ 100,000 / mL
3. Hemoglobin ≥ 9 g/dL
4. Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
5. Serum total bilirubin ≤ 1.5 × ULN
6. Aspartate aminotransferase (AST), (Serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT), and (Serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastasis
7. International Normalized Ratio (INR) and/or Prothrombin Time (PT) ≤ 1.5 × ULN
8. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN
9. Serum Albumin ≥ 3 g/dL measured at two time points: no less than 2 weeks before the 1st dose of misetionamide and within one week prior to the 1st dose. Subjects showing a decrease of \> 20% at the 2nd measurement are excluded.
9. Limited concomitant radiotherapy for pain control is allowed in the 5 weeks prior to initial dose.
10. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test.
11. Subjects must use adequate contraception for the duration of the trial and for at least 3 months after the last dose and refrain from tissue donation during this period. .
12. All acute toxic effects of any prior anti-tumor therapy resolved to Grade \< 1or baseline before start of dosing (exceptions are alopecia and Grade 2 peripheral neuropathy).
Abridged Exclusion Criteria:
1. Diagnosis of any active malignancy other than platinum-resistant ovarian cancer within the past 2 years (not including non-melanoma skin carcinoma, ductal carcinoma in situ of the breast, or carcinoma in situ of uterine cervix treated with curative intent).
2. Subjects has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonia or multiple allergies, clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within \< 6 months prior to the start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or ascites requiring paracentesis in the 4 weeks prior to Screening.
3. Primary refractory disease (defined as failure to achieve at least a partial response (PR) to their initial platinum-based chemotherapy).
4. Radiotherapy (RT) to target lesions, chemotherapy, or other systemic anti-cancer therapy, including prior anti-angiogenic treatment (e.g. bevacizumab) within 4 weeks prior to starting treatment.
5. Ascites including history of therapeutic paracentesis within the 2 weeks prior to signing informed consent.
6. Any other medical, psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate and participate in the trial, or which would interfere with the interpretation of the results.
7. Subject has undergone major surgery, other than diagnostic surgery within 4 weeks prior to Day 1 of treatment in this study.
8. Prior history or current signs of hyphema or glaucoma.
9. History of sickle cell disease or hereditary non-spherocytic hemolytic anemia.
10. Baseline QTc interval \>480 msec for female subjects or \>450 msec for male subjects.
11. Subject is unwilling or unable to comply with study procedures or planning to take a vacation for \>7 consecutive days during the course of the study.
12. First degree relative of the investigator, study staff or the sponsor.
13. Any chemotherapy administered within 3 weeks or 5 half-lives (whichever is shorter) before first dose of misetionamide; other anti-cancer therapy (including surgery, radiotherapy, immunotherapy, hormone therapy, or targeted therapy) administered within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of misetionamide; or within 6 weeks in the case of certain therapies (mitomycin C and nitrosoureas).
14. Investigational therapy administered within 4 weeks or 5-half lives (whichever is shorter) before the first dose of misetionamide.
Axelopran and Nivolumab in PD-1-Refractory Metastatic Melanoma
Axelopran, a peripherally restricted mu-opioid receptor antagonist (PAMORA), is combined with the PD-1 inhibitor nivolumab in patients with PD-1-refractory unresectable or metastatic cutaneous melanoma.
NCT07631325 · Phase 1/2 · John Kirkwood
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed, unresectable or metastatic cutaneous melanoma with documented PD-1-refractory disease, defined as disease progression during or after prior anti-PD-1-based therapy, meeting criteria for either primary or secondary (acquired) resistance, as follows57:
1. Primary resistance: Disease progression as best response, or stable disease lasting \<6 months, following at least 6 weeks (approximately two cycles) of anti-PD-1-based therapy, with progression confirmed by RECIST v1.1.
2. Secondary (acquired) resistance: Disease progression occurring after an initial objective response (complete or partial response) or durable stable disease (≥6 months) per RECIST v1.1 while receiving anti-PD-1-based therapy, or within 12 weeks of discontinuation of anti-PD-1 therapy following prior clinical benefit.
3. Note: Disease must have been histologically confirmed through prior pathology assessment conducted as per SOC.
4. Note: Prior anti-PD-1-based therapy may have been administered as monotherapy or in combination with other agents.
2. Age ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-2
4. Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
5. Patients must have normal organ and marrow function as defined below:
1. absolute neutrophil count ≥1,000/mcL
2. platelets ≥75,000/mcL
3. total bilirubin ≤1.5 × the institutional upper limit of normal (ULN)
4. AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤5 × the institutional ULN for patients with liver metastasis)
5. Creatinine clearance ≥40 mL/min/1.73 m2 for patients with a creatinine level above institutional normal.
6. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and for 5 months after the last dose of treatment (whichever is later). In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
7. Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
a. Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
8. Ability to understand and the willingness to sign a written informed consent document.
9. If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI/CT evaluation done within 28 days of start of study treatment.
Exclusion Criteria:
1. Participant is not a candidate to continue anti-PD-1 therapy due to unresolved toxicities resulting from previous treatment with anti-PD-1 therapy.
2. Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Graves' disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule.
i. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with stable hypothyroidism or Sjogren's syndrome will not be excluded from the study.
ii. Physiological replacement doses of steroids are permitted.
3. Participant is taking a daily dose of opioids that is \>30 morphine milligram equivalents (MME) i. Daily opioid doses ≤30 MME are allowed
4. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
5. Prior malignancy within 2 years that in the investigator's opinion would be likely to affect the outcomes of the patients with unresectable melanoma.
6. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
7. Known HIV or active Hepatitis B or C. Checking viral serology will not be mandated.
8. Patients with major gastrointestinal surgery within 12 weeks prior to the first dose of study treatment. Patients who have a colostomy will be excluded from the trial.
9. Are unable to swallow pills or have known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally.
i. Note: Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
10. Subjects taking moderate to strong CYP3A inhibitors or P-gp inhibitors
Histotripsy in Biliary Tract Cancer
Histotripsy, a non-invasive focused-ultrasound tumor ablation device, is being studied in combination with gemcitabine/cisplatin plus durvalumab or pembrolizumab as first-line treatment for unresectable locally advanced or metastatic biliary tract cancer.
NCT07853690 · Phase N/A · NYU Langone Health
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
Both Cohorts
1. Age \>/= 18 at time of screening
2. Willing and able to provide informed consent for the trial
3. Histologically or cytologically confirmed biliary tract cancer (BTC) including cancers of the intrahepatic bile ducts, extrahepatic bile ducts, and gallbladder
4. Locally advanced or metastatic disease not eligible for resection or transplant
5. RECIST v 1.1 measurable disease
6. No prior systemic therapy for the treatment of locally advanced/metastatic disease a. Recurrent disease after surgical resection must have occurred \>/= 6 months from completion of adjuvant therapy
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
8. Adequate organ and bone marrow function, defined as:
1. Hemoglobin \> 9.0 g/dL
2. Absolute neutrophil count \> 1.5 x 109/L
3. Platelet count \> 100 x 109/L
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN
5. Creatinine within normal limits OR measured creatinine clearance (CL) \>50 mL/min OR calculated creatinine clearance (CL) \>50 mL/min as determined by Cockcroft-Gault
9. Willing and able to undergo general anesthesia and histotripsy procedure
10. A tumor(s) for histotripsy treatment ≤3 cm in longest diameter
1. Note: a maximum of three (3) tumors are allowed to be treated with histotripsy during the index procedure, regardless of how many tumors the subject has
11. Subject has an adequate acoustic window to visualize targeted tumor(s) using ultrasound imaging
Cohort 1 1) Additional organ function as below:
a. Bilirubin \< 1.5 x upper limit of normal (ULN). i. Note: patients with Gilbert's Syndrome may be allowed in consultation with the treating physician and the study PI Cohort 2
1. Additional organ function as below:
a. Bilirubin \> 1.5x ULN due to BTC-related biliary tract obstruction after at least 1 attempt at percutaneous/endoscopic stenting
2. With the exception of hyperbilirubinemia, no contraindication to chemoimmunotherapy
Exclusion Criteria:
Both Cohorts
1. Prior exposure to immune-mediated therapy, including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies
2. History of allogeneic or solid organ transplant
3. Active or prior documented autoimmune disorders. The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia.
2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
3. Any chronic skin condition that does not require systemic therapy.
4. Patients with celiac disease controlled by diet alone.
5. Patients without active disease in the last 5 years may be included but only after consultation with the study PI.
4. Uncontrolled intercurrent illness, including, but not limited to:
a. Ongoing or active infection including but not limited to the below. Patients on prophylactic antibiotics may be eligible after discussion with the study PI.
i. Tuberculosis (tuberculosis testing by local institutional practice is required prior to receipt of chemoimmunotherapy) ii. Hepatitis B (HCV) defined as presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥10 IU/mL (testing is required prior to receipt of chemoimmunotherapy).
1\. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and the absence of HBsAg) are eligible.
iii. Hepatitis C (HCV) defined as positive HCV antibody (testing is required prior to receipt of chemoimmunotherapy).
1\. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
iv. Uncontrolled HIV/AIDS. Testing for HIV 1/2 antibodies is required prior to receipt of chemoimmunotherapy. Patients with known HIV are allowed on study provided they have:
1. A stable regimen of highly active anti-retroviral therapy (HAART)
2. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infection
3. A CD4 count \> 250 cells/mcL
4. An undetectable HIV viral load on standard PCR-based testing b. Symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, MI/TIA/CVA within 3 months prior to study enrollment, uncontrolled cardiac arrhythmia.
c. Active interstitial lung disease (ILD) or history of immune-mediated pneumonitis.
d. Active primary immunodeficiency. e. Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
5\) Other co-morbid disease or condition that would cause undue risk and/or interfere with the conduct or interpretation of the trial in the opinion of the treating investigator 6) Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments of the investigational regimen. Patients whose prior or concurrent malignancy natural history and/or treatment does NOT have the potential to impact safety or study assessments are eligible.
7\) Any unresolved toxicity NCI Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from a previous anticancer therapy, with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment may be included after consultation with the study PI.
8\) Histotripsy-related criteria:
1. Targeted tumor(s) treatment volume overlaps a non-targeted tumor visible via imaging
2. Targeted tumor(s) is not clearly visible with diagnostic ultrasound and computed tomography (CT) or magnetic resonance (MR) imaging
3. Targeted tumor(s) is located in liver segment 1
4. The Planned Treatment Volume intended to cover the targeted tumor includes or encompasses any portion of the main portal vein, common hepatic duct, common bile duct, gallbladder or stomach/bowel.
9\) Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
10\) Subject is pregnant or planning to become pregnant or nursing (lactating). 11) Subjects of reproductive potential who are not willing to use effective birth control from screening to 180 days after the last dose of GCD/P or 90 days after last dose of D/P monotherapy.
12\) Subject is enrolled in another investigational trial and/or is taking investigational medication and/or has been treated with an investigational device \</= 30 days prior to planned procedure date.
Immunotherapy and Nodal-Sparing Irradiation for T-Cell Induction and Unmasking of Tumor Antigenicity in the Microenvironment for Head and Neck Cancer
This phase 2 trial tests pembrolizumab (anti-PD-1 checkpoint inhibitor) induction/adjuvant therapy combined with radiotherapy with or without elective nodal irradiation prior to surgery in resectable, locoregionally advanced HPV-negative HNSCC of the oral cavity or oropharynx.
NCT07773987 · Phase 2 · Medical College of Wisconsin
Recruiting sites: Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Patients 18 years or older.
* Patients with surgically resectable squamous cell carcinoma of the oral cavity or HPV-negative squamous cell carcinoma of the oropharynx. Resectability will be determined by the treating surgeon. Patients must have locoregionally advanced disease defined by clinical T3-4 staging and/or clinical node positive staging.
* A CPS score of at least 1 on initial biopsy.
* Zubrod, or Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Pregnancy. It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
Female patients must meet one of the following:
* Postmenopausal for at least one year before the screening visit, OR
* Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
* If subject is of childbearing potential (defined as not satisfying either of the above two criteria):
* Agree to practice two effective methods of contraception (combination methods requires use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive, intrauterine device, etonogestrel implant, etc.) from the time of signing of the informed consent form through 90 days after the last dose of study agent, AND
* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptom-thermal, post ovulation methods\] and withdrawal are not acceptable contraception methods).
Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
* Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
* Must also adhere to the guidelines of any study-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptom-thermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.) - Ability to understand a written informed consent document, and the willingness to sign it.
Exclusion Criteria:
* HPV-positive squamous cell carcinoma of the oropharynx.
* Tumor inaccessible for clinic-based biopsy as determined by the treating surgeon.
* Solid organ transplant requiring chronic immunosuppression.
* Autoimmune disease requiring use of steroids or chronic immunosuppression.
* Prior invasive malignancy within the past 3 years (except for T1a surgically treated melanoma with negative margins, any early-stage non-melanomatous skin cancer, early-stage prostate cancer, or differentiated thyroid cancer). Patients with benign non-metastasizing tumors are eligible.
* Life expectancy less than 12 months.
* Performance status Zubrod ≥ 3.
* Patients with prior external beam radiation therapy (RT) to the head and neck that overlaps the expected treatment fields.
a. Note: Patients receiving prior Iodine-131 therapy will be eligible.
* Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.
* Body weight ≤ 30 kg.
* Any of the following severe laboratory abnormalities within 30 days of registration, unless corrected prior to it:
1. Sodium \< 125 mmol/L or \> 155 mmol/L
2. Potassium \< 3.5 mmol/L or \> 6 mmol/L
3. Glucose \> 400 mg/dl
4. Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl or \> 12.5 mg/dl
5. Magnesium \< 0.9 mg/dl or \> 3 mg/dl
* Unstable angina and/or congestive heart failure requiring hospitalization within three months of registration.
* Transmural myocardial infarction within three months of registration.
* Medical or psychiatric illness that would compromise the patient's ability to tolerate treatment or limit compliance with study requirements.
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after radiation. This exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding are also excluded.
Neoadjuvant Pembrolizumab and Porustobart in Resectable pMMR/MSS Colon Cancer
A phase 2 trial of neoadjuvant porustobart (an anti-CTLA-4 antibody) plus pembrolizumab (an anti-PD-1 antibody) given before surgery in patients with resectable pMMR/MSS colon cancer.
NCT07808151 · Phase 2 · Solstice Oncology, Inc.
Recruiting sites: California, Florida, Illinois, Maryland, Massachusetts, New York, Ohio, Tennessee, Washington
Read full eligibility criteria
Inclusion Criteria:
≥18 years of age at consent
Adenocarcinoma of the colon (rectosigmoid considered non-rectal); pMMR/MSS status
Any T3 or T4, N any, M0; disease amenable to surgical resection
ECOG Performance Status 0-1
Adequate tumor tissue sample with associated pathology report
Adequate hematologic, hepatic, and renal function
Reproductive status/contraception requirements per protocol
Exclusion Criteria:
Investigational agent within 3 weeks of first dose
Imminent or urgent need for surgery
Prior treatment with ICIs targeting CTLA-4, PD-1, or PD-L1
Systemic corticosteroid/immunosuppressive therapy within 1 week of first dose (exceptions apply)
History of severe hypersensitivity to a fully human mAb; interstitial lung disease; pneumonitis requiring corticosteroids
Active or history of autoimmune disease requiring systemic treatment within 2 years
Major surgery within 4 weeks of first dose; active infection requiring treatment
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
PF-07220060, an oral CDK4 inhibitor, is studied as monotherapy or combined with endocrine therapies (letrozole, fulvestrant, tamoxifen, giredestrant) or enzalutamide in advanced/metastatic HR-positive breast cancer, prostate cancer, NSCLC, colorectal cancer, and liposarcoma.
NCT04557449 · Phase 1/2 · Pfizer
Recruiting sites: California, Connecticut, Massachusetts, Michigan, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria
* Part 1: Breast Cancer (BC)
* Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC
* Part 1A/Part 1D/Part 1E also include: Refractory HR-positive/HER2-positive BC
* Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests
* Part 1F: prostate cancer
* Part 1G: HR-positive/HER2-negative BC
* Part 2A, 2B, 2C, 2E, and 2F: HR-positive/HER2-negative BC
* Part 1D: metastatic castration resistant prostate cancer
* Giredestrant Combination Cohort: ER-positive/HER2-negative BC
* Prior systemic Treatment
* Part 1: HR-positive/HER2-negative BC
* At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator
* HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy
* Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available
* Part 2A and 2E: at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed
* Part 2B: no prior systemic anti-cancer therapies for advanced/metastatic BC
* Part 2C:
* Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or
* Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal
* One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy
* Part 1G and 2F: at least 2 lines of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy
* Giredestrant Combination Cohort: at least 1 (no more than 3) prior line(s) of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy
General Inclusion Criteria
* All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* Adequate renal, liver, and bone marrow function
Exclusion Criteria:
* Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor
* Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
* Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
* Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
* Major surgery or radiation within 4 weeks prior to study intervention
* Last anti-cancer treatment within 2 weeks prior to study intervention; Part 1G and 2F: tamoxifen treatment within 35 days of Day -4
* Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
* Part 1G and 2F: history of or current pulmonary embolism or deep vein thrombosis
* Giredestrant Combination Cohort: history (within 6 months of screening) of or presence of idiopathic symptomatic bradycardia or resting heart rate \<50 bpm at screening
* Pregnant or breastfeeding female participant
* Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease
T Cell Receptor T Cells for Advanced KRAS G12V-mutant Non-small Cell Lung Cancer, Pancreas Cancer, Colon Cancer
FH-A11KRASG12V-TCR, an autologous KRAS G12V-specific TCR-engineered T-cell therapy (with lymphodepleting bendamustine/fludarabine or cyclophosphamide/fludarabine), is being studied in patients with metastatic KRAS G12V-mutant non-small cell lung cancer, pancreatic cancer, or colon cancer.
NCT06043713 · Phase 1 · Fred Hutchinson Cancer Center
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* LEUKAPHERESIS: Diagnosis of metastatic solid tumor
* LEUKAPHERESIS: Tissue confirmation of solid tumor. Confirmation of diagnosis must be or have been performed by internal pathology review of archival biopsy material or other pathologic material at Fred Hutch/University of Washington Cancer Consortium (UWMC)
* LEUKAPHERESIS: HLA-A\*11:01 confirmed through HLA typing at a clinically accredited laboratory
* LEUKAPHERESIS: Previously documented KRASG12V mutation in tumor or plasma cell-free deoxyribonucleic acid (cfDNA) specimens by polymerase chain reaction (PCR) or next-generation sequencing (NGS) test
* LEUKAPHERESIS: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm, unless lymph node in which case short axis must be ≥ 15 mm. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) if clinically indicated, must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast
* LEUKAPHERESIS: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible (these time windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, participants will still be considered for participation, at the discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled. Patients can also refuse biopsies at any time after enrollment
* LEUKAPHERESIS: Participants must be at least two weeks or five half-lives (for small molecules) from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted
* LEUKAPHERESIS: Participants must have progressed on or be intolerant to at least one lines of prior therapy including any targeted therapies indicated for participants with each of the tumor types eligible to enroll, as applicable
* LEUKAPHERESIS: Patients with solid tumors harboring targetable molecular alterations including but not limited to EGFR mutations, ALK, ROS, NTRK fusions, microsatellite instability (MSI)-high, tumor mutational burden (TMB) high, BRAF v600 mutations, HER2 amplifications, must have been treated or refused treatment with applicable targeted therapies, as applicable
* LEUKAPHERESIS: Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last A11KRASG12V-TCR infusion
* LEUKAPHERESIS: 18 years or older at the time of enrollment
* LEUKAPHERESIS: Capable of understanding and providing a written informed consent
* LEUKAPHERESIS: Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
* No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
* LEUKAPHERESIS: No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
* LEUKAPHERESIS: Renal: Creatinine clearance \>= 50 ml/min by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or 24-hour urine clearance
* LEUKAPHERESIS: Hepatic: Total bilirubin \< 2.0 mg/dL
* LEUKAPHERESIS: Hepatic: Aspartate transferase (AST) and alanine transaminase (ALT) \< 5x upper limit of normal (ULN)
* LEUKAPHERESIS: Hepatic: Participants with suspected Gilbert syndrome may be included if total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
* LEUKAPHERESIS: Cardiac: Participants 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and LVEF must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
* LEUKAPHERESIS: Hematologic: Absolute neutrophil count (ANC) \>= 1000 cells/ mm\^3
* LEUKAPHERESIS: Nutrition: Albumin \>= 3 g/dL
* START OF TREATMENT: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm, unless lymph node in which case short axis must be \>= 15 mm. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast
* START OF TREATMENT: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible (these windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, participants will still be considered for participation, at discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled
* START OF TREATMENT: Participants must be at least two weeks from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted
* START OF TREATMENT: ECOG performance status of =\< 1
* START OF TREATMENT: Renal: Creatinine clearance \>= 50 ml/min by CKD-EPI or 24-hour urine clearance
* Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
* START OF TREATMENT: Hepatic: Total bilirubin \< 2.0 mg/dL
* Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
* START OF TREATMENT: AST and ALT \< 5x upper limit of normal (ULN)
* START OF TREATMENT: Participants with suspected Gilbert syndrome may be included if total Bili \> 3 mg/dl but no other evidence of hepatic dysfunction
* START OF TREATMENT: Pulmonary: =\< grade 1 dyspnea and oxygen saturation of arterial blood (SaO2) \>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in the first second (FEVI) \>= 50% of predicted and diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected) \>= 40% of predicted will be eligible
* Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
* START OF TREATMENT: Hematologic: ANC \>= 1000 cells/ mm\^3
* Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
* START OF TREATMENT: Nutrition: Albumin \>= 3 g/dL
* Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
* START OF TREATMENT: Participants with a history of chronic obstructive pulmonary disease (COPD), emphysema, or greater than 30 pack year smoking history should undergo PFTs and meet the following criteria:
* FEVI \>= 50% of predicted and DLCO (corrected) \>= 40% of predicted will be eligible
Exclusion Criteria:
* LEUKAPHERESIS: Prior solid organ transplant or allogeneic hematopoietic stem cell transplant: Kidney transplant participants will be considered on a case-by-case basis requiring discussion with PI. If the participant has had a kidney transplant, participant must have dialysis access, dialysis plan, supportive nephrologist, willingness to stop transplant immunosuppression, and express understanding that rejection is possible outcome. Dialysis or costs related to transplant kidney will not be supported by the study. Participants having had any other solid organ transplants will be excluded, as will those with any history of allogeneic hematopoietic stem cell transplant
* START OF TREATMENT: Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the trial through 4 months after last T-cell infusion. Participants of childbearing potential must have a negative serum pregnancy test within the 2 weeks (14 days) preceding T cell infusion. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)
* START OF TREATMENT: Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI
* START OF TREATMENT: Corticosteroid therapy at a dose equivalent of \> 0.5 mg/kg of prednisone per day. The following treatments are permitted: intranasal, inhaled, topical, or local steroid applications; systemic corticosteroids at physiologic doses equivalent to no more than \> 0.5 mg/kg/day prednisone; steroids as premedication for contrast dye allergy
* START OF TREATMENT: Concurrent use of other investigational anti-cancer agents
* START OF TREATMENT: Active uncontrolled infection: Human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
* START OF TREATMENT: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* START OF TREATMENT: Untreated brain metastases: Participants with small asymptomatic brain metastases (\< 1 cm) or those with brain metastases previously treated and controlled with surgery or radiotherapy will be considered for inclusion at discretion of PI, so long as all other eligibility criteria are met
* START OF TREATMENT: Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 0.5mg/kg/day prednisone per day, unless otherwise approved by PI
* START OF TREATMENT: Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
* START OF TREATMENT: Known allergic reactions to any of the components of study treatments
* START OF TREATMENT: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)
Raludotatug deruxtecan (R-DXd), a CDH6-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor payload, is being studied with or without bevacizumab versus standard chemotherapy in platinum-sensitive, PARP-inhibitor-progressed advanced high-grade ovarian, peritoneal, or fallopian tube cancer after first-line maintenance.
NCT07743164 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: California, Florida
Read full eligibility criteria
The main inclusion criteria include but are not limited to the following:
* Has a histologically or cytologically documented advanced high-grade serous or high-grade endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
* Has received 1 line of platinum-based therapy with a minimum of 4 cycles of platinum-doublet chemotherapy and have platinum-sensitive disease.
* Has received a poly (ADP-ribose) polymerase inhibitor (PARPi) as maintenance treatment after the first line platinum-based chemotherapy course and experienced radiographic progression during treatment or within 42 days of the last dose of PARPi.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization.
* Has recovered from any AEs due to previous anticancer therapies.
The main exclusion criteria include but are not limited to the following:
* Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer.
* Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active GI bleeding within 6 months before randomization.
* Has uncontrolled or significant cardiovascular disease.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of randomization, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), or prior pneumonectomy.
* Has received chronic steroid treatment, with some exceptions.
* Has current, clinically relevant bowel obstruction (including subocclusive disease) including obstruction related to underlying epithelial ovarian cancer, abdominal fistula or GI perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
A Study to Assess Adverse Events, Change in Disease Activity and How Intravenous ABBV-253 Moves Through the Body in Adult Participants With Advanced Solid Tumors
ABBV-253 is an investigational intravenous drug with mechanism not stated in the registry, being tested in a phase 1 dose escalation/optimization study for adults with advanced solid tumors including NSCLC, colorectal, head and neck, pancreatic, gastric/GEJ, biliary tract, and high-grade serous ovarian cancers.
NCT07807956 · Phase 1 · AbbVie
Recruiting sites: Michigan, North Carolina, Texas
Read full eligibility criteria
Inclusion Criteria:
* Part 1 monotherapy dose escalation only: Participants with a diagnosis of a malignant solid tumor by histology (WHO criteria), including, but not limited to non-small cell lung cancer (NSCLC), colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), PDAC, gastroesophageal adenocarcinoma (GEA), ovarian cancer (OC), and biliary tract cancer (BTC)
* ECOG performance status of 0 or 1
* Participants with evaluable and measurable disease per RECIST Version 1.1.
Exclusion Criteria:
* History of other malignancies, with the following exceptions:
* No known active disease present within 3 years prior to first dose of study treatment and felt to be at low risk of recurrence by the treating investigator.
* Adequately treated in situ carcinoma without evidence of disease.
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin without evidence of disease.
* Participants with ovarian cancer with histologies other than high grade serous ovarian cancer including endometrioid, low grade, clear cell, mucinous, or borderline ovarian tumor.
* Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy).
* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids or any evidence of ILD or pneumonitis on Screening chest CT scan.
A Study to Evaluate ATX-898 in Participants With Advanced Solid Tumors
ATX-898, a novel agent whose mechanism is not stated in the registry, is being studied as monotherapy and in combination with fulvestrant and a CDK4/6 inhibitor in advanced solid tumors including recurrent/metastatic HR+ HER2- breast cancer.
NCT07767474 · Phase 1/2 · Antares Therapeutics, Inc
Recruiting sites: Texas, Utah, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Has histologically or cytologically confirmed advanced solid tumor malignancy that is metastatic or locally advanced and unresectable
* Is ≥18 years of age at the time of signing the informed consent form
* ECOG performance status score of 0 or 1
* Adequate organ function
* Must consent to a pre-treatment tumor biopsy (collected during screening or have available archival tumor tissue in the past 5 years.
For Part 1a (monotherapy dose escalation)
* Has received one or more standard systemic therapies and additional standard therapies are either not available, or participant ineligible for available standard therapies For Part 1b (monotherapy dose expansion)
* b1: Has platinum-resistant or refractory metastatic ovarian cancer
* b2: Has recurrent or metastatic gynecologic cancer excluding the cancers eligible for b1
* b3: Has recurrent advanced or metastatic solid tumor excluding the cancers eligible for b1 or b2
* Has at least 1 measurable lesion per RECIST 1.1
For Part 2a (combination dose escalation)
* Has confirmed HR+ HER2 - (including HER2 low and ultra low) status
* Has received prior therapy in the metastatic For Part 2b (combination dose expansion)
* Has confirmed HR+ HER2 - (including HER2 low and ultra low) status
* Treatment-naïve or has received prior therapy in the metastatic setting
Exclusion Criteria:
* Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancer being studied
* Has symptomatic CNS metastases at screening or asymptomatic CNS metastases requiring corticosteroids to control symptoms within 28 days prior to the first dose of ATX-898.
* Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, with the exception of alopecia any grade and Grade ≤2 peripheral neuropathy
* Has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant or would prevent, limit, or confound the protocol-specified assessments
Cohort Specific:
* For abemaciclib cohorts only: has a history of any events of cardiac etiology that would contraindicate dosing with abemaciclib
* For ribocicilib only: has history of pneumonitis or interstitial lung disease
Estrogen to Improve Quality of Life for Men With Newly Diagnosed or Recurrent Metastatic Hormone Sensitive Prostate Cancer, EQUIP Trial
This phase II trial evaluates transdermal estradiol combined with an androgen receptor signaling inhibitor, compared with standard LHRH analogue plus androgen receptor signaling inhibitor, in men with newly diagnosed or recurrent metastatic hormone-sensitive prostate cancer.
NCT07466498 · Phase 2 · Fred Hutchinson Cancer Center
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Must be willing to provide informed consent prior to any study specific procedures
* Age ≥ 18 years
* Documented histologically confirmed adenocarcinoma of the prostate
* Patients must have evidence of newly diagnosed or relapsed metastatic hormone sensitive prostate cancer on CT, positron emission tomography (PET), MRI or bone scan
* No prior chemotherapy for the treatment of hormone sensitive prostate cancer
* No prior therapy with an LHRH analogue or next-generation androgen receptor-signaling inhibitor (e.g. abiraterone, enzalutamide, etc.). Participants may have initiated on a first-generation androgen receptor (AR) antagonist (e.g. bicalutamide) prior to enrollment
* Hemoglobin ≥ 9 g/dL with no blood transfusion in the past 28 days (measured within 30 days prior to administration of study treatment)
* Platelet count ≥ 100 x 10\^9/L (measured within 30 days prior to administration of study treatment)
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (measured within 30 days prior to administration of study treatment)
* Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) or serum glutamic pyruvate transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal (measured within 30 days prior to administration of study treatment)
* Patient must have creatinine clearance estimated using the Cockcroft-Gault equation (measured within 30 days prior to administration of study treatment)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) with exception for Gilbert's syndrome (measured within 30 days prior to administration of study treatment)
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Patients must have a life expectancy ≥ 16 weeks
* Patients must be willing and able to comply with protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, MRI and/or bone scan and is suitable for repeated assessment. Subjects without bone metastases must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner
Exclusion Criteria:
* Involvement in the planning and/or conduct of the study
* Other malignancy unless curatively treated with no evidence of disease for ≥ 2 years. Exceptions include adequately treated non-melanoma skin cancer or non-muscle invasive bladder cancer
* Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patient with spinal cord compression unless considered to have received definitive therapy for this and evidence of clinically stable disease for 28 days
* Patients considered inappropriate to receive docetaxel chemotherapy by their treating provider
* Use of corticosteroids at a dose equivalent to \> 10 mg of prednisone daily
* Planning to receive concurrent treatment with another systemic cancer therapy, aside from an LHRH analogue
* Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure \[BP\] ≥ 165/100), unstable spinal cord compression, superior vena cava syndrome or extensive interstitial lung disease
* Patients with a known hypersensitivity to transdermal estradiol, LHRH analogue, ARSIs or any of the excipients of these products
* Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through body or other body fluids
* Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
* Any psychological, familial, sociological or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
* Evidence of a pre-existing condition that, in the opinion of the investigator, would put the patient at risk from estradiol therapy.
* Some examples include: history of blood clotting disorder, migraines with aura or other focal neurological symptom, angina (New York Heart Association grade III or higher)
* Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation
* Excluded due to risk of venous thromboembolism from hormone supplementation
* Patients with New York Heart Association (NYHA) class III or IV heart failure or history of a prior myocardial infarction (MI) or cerebrovascular accident (stroke or transient ischemic attack) within 5 years of enrollment to the study
* Excluded due to increased risk of cardiovascular events with estradiol supplementation
T-DXd Based Therapy Followed by Endocrine Therapy Plus Dual HER2 Blockade in First-line HER2+/ HR+ Metastatic Breast Cancer and Retreatment With T-DXd
This phase 3 trial tests a sequential strategy of upfront trastuzumab deruxtecan (HER2-targeted antibody-drug conjugate) plus pertuzumab followed by maintenance dual HER2 blockade with endocrine therapy and palbociclib, with T-DXd retreatment at progression, in first-line HER2-positive/HR-positive advanced or metastatic breast cancer.
NCT07683754 · Phase 3 · Daiichi Sankyo
Recruiting sites: Maryland, Nevada, Tennessee, Texas
Read full eligibility criteria
Key Inclusion Criteria for Upfront Treatment Phase
1. Sign and date the Main Trial informed consent form (ICF), prior to the start of any trial-specific procedures.
2. Participant must be ≥18 years of age at the time the ICF is signed.
3. Have pathologically documented breast cancer that:
* Is locally advanced and unresectable or metastatic (participants who can be treated with curative intent are not eligible).
* Participant must have histologically confirmed HER2+ and HR+ (ER+ and/or PR+), mBC. ER, PR, and HER2 measurements should be locally performed according to institutional guidelines.
* Is documented by local testing as HR-positive (either ER and/or PgR positive \[ER or PgR ≥1%\]) per ASCO/CAP guidelines in the metastatic setting or from the primary tumor with the latest sample available.
4. Has not received prior chemotherapy or HER2-targeted therapy for mBC. Participant who has received chemotherapy or HER2-targeted therapy or radiotherapy or surgery in the neoadjuvant or adjuvant setting are eligible, with a DFI of \>6 months (\>183 days) from completion of systemic chemotherapy or any HER2-targeted therapy (antibody, TKI or T-DM1) to diagnosis of advanced or metastatic disease.
5. ECOG PS of 0 or 1 assessed no more than 3 days prior to initiation of trial intervention.
6. Has at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI, which is suitable for accurate repeated measurements, or nonmeasurable, bone-only disease that can be assessed by CT, MRI, or X-ray.
7. Participant with brain metastases are allowed if participant is asymptomatic and does not require immediate local intervention.
Additional Key Criteria to Transition into the Maintenance Treatment Phase
1\. Participant transitioning into the Maintenance Treatment Phase must meet the following inclusion criteria for Maintenance Treatment:
* Participant is without evidence of disease progression under T-DXd + pertuzumab treatment by local assessment according to RECIST v1.1 (ie, CR, PR, or SD), and
* Participant is willing to switch therapy, and
* Participant completed at least 8 cycles of T-DXd + pertuzumab and achieved cCR (confirmation of CR should be obtained during the next protocol defined scheduled tumor assessment.), or
* Participant completed 18 cycles (in total) of T-DXd and achieved a SD or PR, and the last 2 scans showed no further tumor shrinkage (defined as 2 subsequent scans at least 6 weeks apart) or has an unconfirmed CR.
Additional Key Criteria for T-DXd Retreatment Phase
1. Has received at least 1 dose of Maintenance Treatment.
2. Has documented disease progression per RECIST v1.1 per investigator assessment during Maintenance Treatment.
3. Participant who experienced ILD Grade 1 during the Maintenance Treatment Phase, must have fully resolved before starting T-DXd during the Retreatment Phase.
Key Exclusion Criteria for Upfront Treatment Phase
1. Has prior therapy with any CDK inhibitor.
2. Previous T-DXd therapy for early BC with an EFS or disease-free interval of \< 12 months from completion of T-DXd therapy in the neoadjuvant or post-neoadjuvant setting.
Key Exclusion Criteria for Maintenance Treatment Phase
1. Is receiving concurrent therapy with other trial interventions (except pertuzumab which is part of Upfront Treatment and Maintenance Treatment).
2. Has prior therapy with any CDK inhibitor.
3. Has any unresolved SAE related to prior T-DXd + pertuzumab treatment from the Upfront Treatment Phase, defined as an event that has not resolved to baseline by the time of the eligibility assessment for the Maintenance Treatment Phase.
4. Has experienced Grade 3 or 4 ILD/pneumonitis during the Upfront Treatment Phase.
5. Has spinal cord compression or clinically active CNS metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
Key Exclusion Criteria for T-DXd Retreatment Phase
1. Participant who developed ILD/pneumonitis Grade ≥2 during the Upfront Treatment Phase or Maintenance Treatment Phase.
2. Participant has any unresolved SAE related to prior Maintenance Treatment Phase therapies defined as an event that has not resolved to baseline by the time of the eligibility assessment for the T-DXd Retreatment Phase.
3. Participant who developed non-ILD toxicities related to T-DXd in the Upfront Treatment Phase that required T-DXd discontinuation.
TOP 2301: Neoadjuvant Chemo for NSCLC
Alirocumab, a PCSK9-targeted monoclonal antibody, is being added to neoadjuvant platinum-doublet chemotherapy plus the PD-1 inhibitor cemiplimab in patients with resectable stage IB-IIIA non-small cell lung cancer prior to surgery.
NCT06385262 · Phase 2 · Duke University
Recruiting sites: North Carolina
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥ 18 years.
2. Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Patient is eligible to enroll in the study based on clinical suspicion of NSCLC but are required to have a histological diagnosis of NSCLC in order to be eligible to receive treatment on study.
3. Clinical stage IB, IIA/IIB, or III (N0-2) amenable to surgical resection.
4. Agrees to research blood collections for study.
5. Deemed a surgical candidate.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. No prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer.
8. Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
9. No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
10. Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines.
11. Sexually active males and females of reproductive potential must agree to use an appropriate contraceptive method during the study and for 120 days following the last dose of study drug.
12. Females of childbearing potential must test negative for pregnancy within 48 hours prior to any initial study procedure based on a serum pregnancy test. (If subject uses appropriate contraceptive methods from the time of the initial serum pregnancy test, then the subsequent pregnancy test can be done within 72 hours prior to start of study treatment. If appropriate contraceptive measures are not begun immediately with the first serum pregnancy test, then subsequent serum pregnancy tests must be done within 48 hours prior to the start of study treatment.)
13. Adequate organ function defined as:
1. Absolute neutrophil count (ANC) ≥ 1500 per uL
2. Platelets ≥ 100,000 per uL
3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or growth factor dependency (within 7 days of assessment)
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN
5. Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
6. Aspartate aminotransferase (AST) \[serum glutamic-oxaloacetic transaminase (SGOT)\] and alanine aminotransferase (ALT) \[glutamic-pyruvic transaminase (SGPT)\]≤ 2.5 x ULN
7. Albumin ≥ 2.5 mg/dL
8. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants
9. Activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants
Exclusion Criteria:
1. Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
2. Participants with known EGFR mutations, ALK translocation, or ROS1 translocation. If testing is done, an FDA-approved assay should be used.
3. Known history of active TB (Bacillus Tuberculosis).
4. Hypersensitivity to alirocumab or any of its excipients.
5. Concurrent administration of any other anti-tumor therapy.
6. Prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent.
7. Therapy with an anti-PCSK9 agent within 90 days of study entry.
8. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
9. Inability to comply with protocol or study procedures.
10. Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
11. Known history of, or any evidence of active, non-infectious pneumonitis.
12. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or HCV infection; or diagnosis of immunodeficiency. Exceptions:
1. Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
2. Patients with HBV (hepatitis B surface antigen positive) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted.
3. Patients who are HCV antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
13. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc.) is not considered a form of systemic treatment. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g. Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
14. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
15. Known additional invasive malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy in situ cervical cancer.
16. Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
17. Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant disorders that in the opinion of the investigator would compromise the safety of the patient or compromise the patient's ability to complete the study.
18. Any non-oncology, live vaccine therapy used for prevention of infectious diseases within 30 days prior to start of study treatment.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. Coronavirus Disease 2019 (COVID-19) vaccines are also allowed.
19. Myocardial infarction having occurred less than 6 months prior to study enrollment, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications. Patients with coronary artery disease treated with surgery and/or stent \> 6 months ago, if stable without symptomatic angina pectoris, active ischemia are eligible.
20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
21. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either psychiatric or physical (e.g., infectious) illness.
This is a Phase 1/1b Study to Evaluate the Safety and Preliminary Antitumor Activity of LTZ-232 in Participants With Advanced/Metastatic Colorectal Cancer and Other Solid Tumors
LTZ-232, an intravenous agent whose registry listing associates it with EpCAM (exclusion criteria bar prior EpCAM-targeting therapy), is being tested as monotherapy in a first-in-human Phase 1/1b trial for advanced/metastatic colorectal cancer and other solid tumors that have failed standard therapy.
NCT07878988 · Phase 1 · LTZ Therapeutics, Inc.
Recruiting sites: Arizona
Read full eligibility criteria
Inclusion Criteria:
* Advanced /metastatic colorectal tumors that have failed standard treatments
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
* Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1
* Adequate organ function based on laboratory testing
Exclusion Criteria:
* Active infection with hepatitis B or C
* Uncontrolled CNS metastases
* Active autoimmune disease
* Clinically significant cardiovascular disease not adequately controlled with medication or impaired function
* Previous treatment with EpCAM targeting agent
* Pregnant or breast feeding
* Non-colorectal active malignancy within 3 years that could interfere with study interpretation
Torvutatug Samrotecan With or Without Bevacizumab as Maintenance Treatment of Platinum-sensitive Relapsed Epithelial Ovarian Cancer
Torvutatug samrotecan, a folate receptor alpha (FRα)-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor, is being studied with or without bevacizumab as maintenance therapy versus standard of care in platinum-sensitive relapsed epithelial ovarian, fallopian tube, or primary peritoneal cancer.
NCT07816666 · Phase 3 · AstraZeneca
Recruiting sites: Alaska, Florida, Indiana, Louisiana, Maryland, Michigan, New York, Ohio, Oklahoma, Pennsylvania, Texas, Utah, Virginia, West Virginia
Read full eligibility criteria
Inclusion Criteria:
* Participants with confirmed histology of high-grade epithelial serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer.
* Provision of an archival FFPE tumour sample
* Participants who received at least one, and no more than 2 lines of prior systemic anticancer therapy.
* Participants with radiologically confirmed disease relapse ≥ 6 months after their last platinum chemotherapy infusion in the previous line of treatment
* Participants who received 4-6 cycles of PBC during the induction phase of their current line of treatment.
* Participants assigned to bevacizumab must have received a minimum of 3 cycles of bevacizumab with 3 cycles of PBC prior to randomisation.
* Participants with non-progressive disease upon completion of PBC in their current line of treatment.
* Participants with documented BRCA mutation 1/2 must have received prior PARP inhibitor (unless ineligible due to contraindications, precautions, or intolerance).
Exclusion Criteria:
* Participants with tumours of non-epithelial origin, borderline tumours, clear cell OC, mucinous OC, carcinosarcoma, or low-grade epithelial tumours.
* Participants with history of (non-infectious) ILD/pneumonitis that required steroids, or supplemental oxygen, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
* Participants with non-healing wound, active ulcer, or bone fracture (not applicable if not receiving bevacizumab)
* Participants with evidence of active or ongoing bowel obstruction (not applicable if not receiving bevacizumab)
* Participants with prior exposure to any FRα-targeted therapy, including MIRV, or any TOP1i Antibody-drug Conjugate (ADC)
A Phase 1 Dose-escalation Study of UGN-501 Administered Intravesically in Adult Participants With Recurrent NMIBC
UGN-501 is a biologic agent of unstated mechanism administered intravesically as induction and maintenance therapy in adults with recurrent non-muscle invasive bladder cancer.
NCT07725796 · Phase 1 · UroGen Pharma, Inc., a subsidiary of UroGen Pharma Ltd.
Recruiting sites: Arizona, California, Colorado, Florida, Massachusetts, Michigan, Nebraska, New York, Oregon, Pennsylvania, South Carolina, Texas
Read full eligibility criteria
Inclusion Criteria:
1. Participant must be 18 years of age or older at the time of signing informed consent.
2. Has confirmed recurrent non-muscle invasive bladder cancer (NMIBC) with high-grade Ta and/or T1 disease and/or carcinoma in situ (CIS), or recurrent low-grade Ta and/or T1 disease.
3. Participants with high-grade Ta and/or T1 disease and/or CIS must meet one of the following criteria:
* Has BCG-unresponsive disease, defined as:
* persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy; or
* recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy; or
* high-grade T1 disease at the first evaluation following a BCG induction course.
Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course. Participants with BCG-unresponsive disease also must be unwilling or unfit to undergo radical cystectomy.
* Is BCG-exposed, defined as high-grade persistent or recurrent NMIBC within 24 months of the last dose of BCG but not meeting the definition of BCG-unresponsive disease, and received at least 5 of 6 doses of an initial induction course of BCG.
* Is BCG intolerant, defined as the inability to tolerate at least 1 full induction course of BCG.
* Has a high-grade Ta tumor ≤3 cm and failed at least 1 previous course of therapy, such as TURBT plus an adjuvant induction course of intravesical chemotherapy.
4. Participants with low-grade disease must meet one of the following criteria:
* Ta tumors recurring within 1 year.
* Ta solitary tumor \>3 cm.
* Ta multifocal tumors.
* T1 tumors.
5. All visible papillary tumors must be resected and obvious areas of CIS fulgurated during Screening or within 6 weeks before Screening. Participants with T1 disease should have a re-staging TURBT during Screening or within 6 weeks before Screening. Enhanced cystoscopy, such as blue light cystoscopy or other locally accepted modalities, is permitted, but the same modality must be used for all subsequent disease assessments.
6. Has Eastern Cooperative Oncology Group performance status score ≤2.
7. Has no concomitant upper tract urothelial carcinoma (UTUC) or urothelial carcinoma within the prostatic stroma. Freedom from upper tract disease, if clinically indicated, must be demonstrated by no evidence of upper tract tumor by either IV pyelogram, retrograde pyelogram, CT urogram with or without contrast, MRI urogram with or without contrast, or ureteroscopy with ureteral washing for cytology, performed within 6 months of enrollment. Participants with urothelial carcinoma involving the prostatic urethra, where carcinoma is confined to the ducts and/or epithelium, may be included after a restaging TURBT is performed to rule out more extensive disease involving the prostatic stroma.
8. Participants with prostate cancer may be eligible if, after surgery or radiation, they do not meet criteria for biochemical recurrence, or if they are on active surveillance at very low, low, or favorable risk for progression, defined as Gleason Grade Group 1 or 2, Gleason score ≤7, prostate-specific antigen \<20 ng/dL, and cT1-cT2b, at the discretion of the investigator.
9. Has adequate organ and bone marrow function within 14 days of treatment initiation, as determined by routine laboratory tests:
* Leukocytes ≥3000/μL.
* Absolute neutrophil count ≥1500/μL.
* Platelets ≥100,000/μL.
* Hemoglobin ≥9.0 g/dL.
* Total bilirubin ≤1.5 × upper limit of normal (ULN).
* Aspartate aminotransferase (AST) ≤2.5 × ULN.
* Alanine aminotrasferase (ALT) ≤2.5 × ULN.
* Alkaline phosphatase ≤2.5 × ULN.
* Estimated creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation.
10. Has a life expectancy \>12 months.
11. Participants and participant partners must agree to follow contraception and barrier method requirements consistent with local regulations and the protocol during the study intervention period and for at least 12 weeks after the last study intervention instillation.
12. Is willing and able to sign informed consent and comply with the requirements and restrictions listed in the informed consent form and protocol.
Exclusion Criteria:
1. Current or previous evidence of muscle invasive, locally advanced nonresectable, or metastatic urothelial carcinoma, including T2, T3, T4, and/or stage IV disease.
2. Current systemic therapy for bladder cancer.
3. Prior treatment with any human adenovirus-based therapy, such as nadofaragene firadenovec-vncg or cretostimogene grenadenorepvec.
4. Intravesical therapy within 4 weeks before starting study intervention, including but not limited to BCG, chemotherapy, and nogapendekin alfa inbakicept.
5. Participation in a study of an investigational agent with receipt of study therapy, or receipt of an investigational device, within 4 weeks before the first dose of study intervention.
6. Receipt of immune modulator therapy within 5 half-lives of starting study intervention, including but not limited to pembrolizumab, BCG, and nogapendekin alfa inbakicept.
7. Receipt of a vaccine or anti-viral agent within 2 weeks before starting study intervention.
8. Active infection requiring systemic therapy, including urinary tract infection. Participants may enter the study once the infection is satisfactorily treated.
9. Immunocompromised state, including but not limited to HIV infection or any condition that required systemic immunosuppressive treatment in the past 2 years, such as active systemic autoimmune disease or solid organ or stem cell transplant. Short courses (≤14 days) of steroids for medical reasons without anticancer intent, such as atopic dermatitis, psoriasis, infection, or allergic reaction, are permitted if the last dose was at least 4 weeks before the first dose of study intervention.
10. Any medical, psychological, familial, sociological, or geographical condition that, in the opinion of the investigator, would preclude participation in the study.
11. History of malignancy of another organ system within the past 5 years, except previously treated UTUC, basal cell carcinoma or squamous cell carcinoma of the skin, and/or prostate cancer meeting protocol-specified criteria.
12. Cannot tolerate intravesical dosing or intravesical surgical manipulation.
13. Known allergy or hypersensitivity to any of the study interventions or any study intervention excipients.
A Study Evaluating the Immunotherapy Treatment for Ovarian Cancer and Other Advanced Malignancies.
NY-ESO-1 TCR/dnTGFβRII gene-modified T cell therapy (with decitabine/cyclophosphamide conditioning and aldesleukin support) is being studied in NY-ESO-1-expressing advanced/metastatic ovarian, fallopian tube, or primary peritoneal carcinoma after prior standard therapy.
NCT07389239 · Phase 1/2 · University of Chicago
Recruiting sites: Illinois
Read full eligibility criteria
Inclusion Criteria:
* Adult subjects (18 years and older) with histologically or cytologically of advanced (metastatic or inoperable) advanced solid tumors.
* Tumor (either an archival specimen or a fresh biopsy) shows NY-ESO-1 expression of 1+ by IHC (H-score). NY-ESO-1 expression must be confirmed by central validated assay.
* Patients with NY-ESO-1 expressing solid tumors will be included. Patients must have received, been intolerant of, or been ineligible to receive at least 2 lines of the current standard of care therapy including but not limited to chemotherapy, immunotherapy and/or targeted therapy when appropriate (e.g. Atezolizumab is approved for use in patients with alveolar soft part sarcoma) according to their disease:
* Inoperable or metastatic (advanced) ovarian, primary peritoneal or fallopian tube carcinoma:
* Has received platinum containing chemotherapy and has platinum refractory or resistant disease that has progressed on second line therapy
* If platinum sensitive disease, should have received ≥2 lines of chemotherapy.
* May have received PARP inhibitors, bevacizumab or other targeted VEGF inhibitor therapy
* Inoperable or metastatic (advanced) soft tissue sarcoma:
* Subjects must have previously received either an anthracycline or ifosfamide containing regimen.
* Gastrointestinal stromal tumors are eligible, but only must have previously received KIT-targeted therapy if a sensitizing mutation is present.
* Angiosarcomas are eligible, but only must have received prior taxane-based chemotherapy
* Urothelial carcinoma:
* Subjects must have received or refused 1 prior platinum-based therapy for the treatment of metastatic or locally advanced unresectable disease.
* Subjects who are not eligible for a platinum-containing regimen or who have progressed on a platinum-containing regimen
* Subjects may have received an anti-PD-l/PDL1 checkpoint inhibitor
* Metastatic castration-resistant adenocarcinoma of the prostate (CRPC) defined as serum testosterone level ≤ 50 ng/dL with prior surgical castration or ongoing androgen deprivation, with progressive disease:
* Progressive disease is defined by rising prostate specific antigen (PSA) or radiographic imaging according to the PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
* At least one prior chemotherapy regimen in the metastatic setting
* Prior therapy with at least one standard 17α lyase inhibitor or second generation anti-androgen therapy for the treatment of castrate- resistant prostate cancer.
* Breast Cancer
* Prior standard of care regimens with at least one anthracycline or taxane-based regimen in either an adjuvant or metastatic setting unless intolerant or clinically not indicated. For ER positive HER2 negative cancer must have progressed on therapy with CDK 4/6 inhibitor combination. Prior hormonal therapy or Human epidermal growth factor receptor-2 (HER2) targeted therapies are allowed.
* Melanoma
* A PD-1 or PD-L1 inhibitor (with or without a cytotoxic T lymphocyte-associated protein 4 \[CTLA-4\] inhibitor). Patients with an actionable mutation (e.g., BRAF) must have received at least one targeted therapy.
* Non-small cell lung cancer
* A PD-1 or PD-L1 inhibitor and for patients with a PD-L1 tumor proportion score (TPS) \< 50%, a platinum-based chemotherapy regimen. Patients with non-squamous NSCLC with an actionable mutation (e.g., EGFR, ALK, ROS-1) must have received at least one targeted therapy. A checkpoint inhibitor is not required for patients with actionable mutations.
* Additional advanced solid tumor expressing NY-ESO-1 are included. Patients must have received a minimum of one prior therapy.
* Subjects who are intolerant to required prior therapies must have previously received at least one systemic therapy that was deemed ineffective by the treating physician.
* At screening, must have tissue available for NY-ESO-1 testing (if not previously performed) or be willing and able to undergo a fresh tissue biopsy.
* HLA-A\*0201 (HLA-A2.1) positivity by molecular subtyping (blood test or buccal swab, historical documentation acceptable).
* Age ≥ 18 years old.
* Life expectancy greater than 3 months assessed by a study physician.
* Have been informed of other treatment options.
* A minimum of one measurable lesion defined as meeting the criteria for measurable disease according RECIST1.1 criteria.
* No restriction based on prior treatments provided they have discontinued therapy at least 4 weeks prior to starting study treatment. Lesions amenable to radiotherapy or palliative radiotherapy (e.g.- bone metastases or metastases causing nerve impingement) should be treated \> 4 weeks prior to enrollment and patients must be fully recovered from the effects of radiation prior to receiving the investigational agent and that patients must not receive radiation while enrolled on this study.
* Patients must have received prior anti-cancer treatment(s) or an investigational product(s) within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment(s) AND unresolved or unstable serious toxic side-effects of prior chemotherapy/treatment must have recovered to Grade 1 per CTCAE (v5.0)
* Must have adequate venous access for apheresis and must be willing to and able to go through the procedure.
* Women of childbearing potential must agree to use effective methods of birth control for the duration of the study and 6 to 12 months after until persistence of the study drug is no longer detected in the peripheral blood. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception. It is recommended that a combination of two methods be used.
* ECOG performance status ≤1 (Karnofsky ≥80%, see Appendix A).
* Patients must have normal organ and marrow function as defined below:
* leukocytes ≥3,000/mcL
* absolute neutrophil count ≥1,000/mcL
* platelets ≥100,000/mcL
* total bilirubin ≤1.5 × ULN (institutional upper limit of normal)
* AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (institutional upper limit of normal)
* creatinine ≤2 × ULN (institutional upper limit of normal) OR
* creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels \> 2 × ULN
* Patient must understand the investigational nature of this study and be willing to sign a written informed consent form prior to receiving any study related procedure.
* Participant must agree to and arrange for a caregiver (age ≥ 18 years old) available 24 hours a day/ 7 days a week and arrange for lodging within 45 minutes-drive to UChicago and transportation for a period of time after discharge from the hospital. The exact amount of time will depend on the individual status as determined by the treating physician.
Exclusion Criteria:
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study.
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure with New York Heart Association class III or IV disease, patients with a LVEF \< 45%, a myocardial infarction within 6 months prior to study entry or a history of myocarditis, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active autoimmune disease requiring doses of corticosteroids of ≥ 10 mg/day of prednisone (or its equivalent) or other immunosuppressive treatments.
* History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin.
* Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses or isolated use of steroids as premedication for medical procedures to minimize allergic reaction \[e.g. CT scan dye\] are allowed).
Known cases of clinically active brain metastases (brain MRI as clinically indicated) because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment.
* Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
* Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal for two years,or must agree to use effective contraception during the period of treatment and after as stated in inclusion 3.1.9. Patients with reproductive potential must have a negative pregnancy test (serum/urine) within 48 hours from starting the conditioning chemotherapy.
* Lack of availability of a patient for immunological and clinical follow-up assessment.
* Patients with pulmonary function test abnormalities as evidenced by a FEV1/FVC\<70% of predicted for normality will be excluded.
* Patients with baseline O2 saturation \<90% on room air.
* Patients with history of pneumonitis and/or interstitial lung disease.
* Patients with ascites, pleural or pericardial effusions which requires repeated (2 within 4 weeks) or continuous paracentesis, thoracentesis or pericardiocentesis within last 2 months.
* Patients that have had "any major surgical procedure (planned or anticipated) within 4 weeks from the first dose of study treatment(s).
* Patients who have received any live vaccines within 30 days prior to enrollment.
A Study of Sovilnesib in Subjects With Ovarian Cancer
Sovilnesib, an oral small-molecule KIF18A inhibitor, is being studied as monotherapy in a phase 1b dose-finding trial for platinum-resistant/refractory high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.
NCT06084416 · Phase 1 · Volastra Therapeutics, Inc.
Recruiting sites: Alabama, Arkansas, California, Georgia, Maryland, Massachusetts, New York, Oklahoma, South Carolina, Washington
Read full eligibility criteria
Key Inclusion Criteria:
* All Parts: Age ≥ 18 years, ECOG Performance Status ≤ 1, at least 1 site of measurable disease evaluable by CT scan or MRI per RECIST 1.1, able to take oral medication without alteration
* Histologically confirmed locally advanced, inoperable, or metastatic tumor.
* High Grade Serous Ovarian Cancer, Fallopian Tube or Primary Peritoneal Cancer - histologically confirmed; locally advanced, inoperable or metastatic; p16 positive (Part 2 only); platinum resistant (defined as radiographic progression/recurrence \<180 days after last dose of ≥ 4 cycles of platinum containing therapy) or refractory; prior bevacizumab treatment, unless ineligible or intolerant; if germline and/or somatic BRCA1/2 mutation, previously treated with PARP-inhibitor (unless ineligible or intolerant).
Key Exclusion Criteria:
* Part 1 only: MSI-H, dMMR, POLE gene hotspot mutated, or known hypermutator phenotype
* Endometrioid, clear cell, mucinous, sarcomatoid, low-grade/borderline ovarian tumor or mixed tumors containing any of the above histologies
* Previously received KIF18A inhibitor
* Leptomeningeal disease, or new or progressive CNS metastases or spinal cord compression
* Cardiac parameters: MI, PE, CABG, severe/unstable angina or stroke ≤ 6 months, NYHA Class ≥ II, LVEF \< 50%
* Any gastrointestinal condition (e.g. malabsorption syndrome, surgical anastomosis, short bowel syndrome) that might affect the absorption of oral medications including the study drug
A Study to Assess Adverse Events and Change in Disease Activity With Treatment Combinations With Telisotuzumab Adizutecan in Adults Participants With Pancreatobiliary Cancers
Telisotuzumab adizutecan, a c-Met-targeted antibody-drug conjugate carrying a topoisomerase-inhibitor payload, is being studied in combination with gemcitabine (versus gemcitabine plus nab-paclitaxel standard of care) in adults with pancreatobiliary cancers, including pancreatic ductal adenocarcinoma.
NCT07769502 · Phase 2 · AbbVie
Recruiting sites: Mississippi
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 or 1.
* Resolution of any acute clinically significant treatment-related toxicity from prior therapy to Grade \<= 1 prior to study entry (except for alopecia of any grade).
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Exclusion Criteria:
* Prior cellular-Mesenchymal Epithelial Transition (c-MET) protein targeting therapy
* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan, including a history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis.
* Has had major surgery or significant traumatic injury within 28 days prior to randomization/enrollment, or anticipation of the need for major surgery during the course of study intervention. Placement of biliary stent/tube is permitted.
A Study to Assess Zipalertinib Versus Placebo in Participants With Early Stage NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection
Zipalertinib, an oral EGFR tyrosine kinase inhibitor targeting uncommon EGFR mutations including exon 20 insertions, is being studied versus placebo as adjuvant therapy in early-stage NSCLC following complete tumor resection.
NCT07128199 · Phase 3 · Taiho Oncology, Inc.
Recruiting sites: Alaska, California, District of Columbia, Florida, Georgia, Illinois, Michigan, New Jersey, New York, North Carolina, Ohio, South Carolina, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
2. Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendment (CLIA) certified (United States \[US\]) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt:
1. exon20 insertion mutations (ex20ins) or
2. other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) exons 18-21 of the EGFR tyrosine kinase domain
3. Baseline imaging assessment of the brain (MRI \[preferred modality\] or CT scan) performed within 8 weeks prior to randomization must show no evidence of brain metastasis
4. Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.
5. Complete recovery from surgery, including post-operative wound healing, and prior adjuvant chemotherapy (if applicable) at the time of randomization. Randomization timing is defined as follows:
1. For participants without prior adjuvant chemotherapy: 4 weeks and 12 weeks following surgery.
2. For participants with prior adjuvant chemotherapy: 4 weeks and 8 weeks after the last dose of adjuvant chemotherapy.
6. Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
7. Pathologic (post-operative) Stage IB, IIA, IIB, or IIIA according to the AJCC 9th tumor nodes metastasis (TNM) staging system for lung cancer. In addition, participants with stage IIIB are eligible when regional lymph node involvement is N2.
8. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Exclusion Criteria:
1. Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research.
2. Treatment with any of the following within the time frame specified:
1. Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time.
2. Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
3. Any prior systemic anticancer therapy for NSCLC, including preoperative (neoadjuvant) chemotherapy, immunotherapy, or investigational therapy. (Exception: Participants who have received postoperative adjuvant platinum-based chemotherapy up to 4 cycles are permitted)
4. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study treatment.
5. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
3. Has received only wedge resections (complete anatomic segmentectomy is acceptable).
4. Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
5. Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).
6. Has a history of any other cancer except for any of the following:
1. Non-melanoma skin cancer treated with curative intent
2. Carcinoma in situ treated with curative intent
3. Other curatively treated cancer, with no evidence of disease for \>3 years following the end of treatment and, in the opinion of the treating physician, has no substantial risk of recurrence.
4. Concurrent malignancy of which natural history does not have the potential to interfere with the safety or efficacy assessment (eg, Gleason 6 prostate cancer)
7. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.
8. Active bleeding disorders.
9. Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.
A Study to Test Obrixtamig in Combination With Pumitamig in People With Advanced Small Cell Lung Cancer (Dareon®-Rosetta35)
Obrixtamig (a DLL3xCD3 bispecific T-cell engager) plus pumitamig (a PD-L1xVEGF-A bispecific antibody), with or without carboplatin/etoposide chemotherapy, is being studied in patients with extensive-stage small cell lung cancer, both previously treated and treatment-naive.
NCT07843940 · Phase 1/2 · Boehringer Ingelheim
Recruiting sites: Florida, Massachusetts, New Jersey, New York, Tennessee
Read full eligibility criteria
Inclusion criteria:
1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
2. Male or female participants ≥18 years old and at least at the legal age of consent in countries where it is greater than 18 years at the time of signature of the Informed Consent Form (ICF).
3. Willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, laboratory tests, restrictions regarding prohibited medications, lifestyle restrictions, and other requirements related to the trial. This includes that they are able to understand and follow trial-related instructions.
4. Histologically or cytologically confirmed Extensive Stage Small Cell Lung Carcinoma (ES-SCLC) \[using the AJCC (American Joint Committee on Cancer) tumour node metastasis staging system combined with Veterans Administration Lung Study Group (VALG)'s two stage classification scheme\].
5. Prior systemic anti-cancer treatment for ES-SCLC:
* For Cohort 1 - must have received at least one line of platinum-containing treatment but no more than 2 lines of treatment per local standard of care for the treatment of ES-SCLC.
* For Cohort 2 - must have received no prior systemic therapy for ES-SCLC. Participants with prior chemoradiotherapy for limited stage (LS)-SCLC must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last chemotherapy, radiotherapy, or chemoradiotherapy before diagnosis of ES-SCLC to be eligible.
6. At least one measurable lesion outside of the Central Nervous System (CNS) as defined per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Previously treated lesions after local therapy (radiotherapy, ablation, interventional procedures, etc.) are generally not considered target lesions. If the lesion with prior local treatment is the only measurable lesion, radiologic evidence must be provided to demonstrate disease progression for selection as target lesion (an isolated blastic bone metastasis or a singular central nervous system metastasis should not be considered as a measurable lesion).
7. Availability of an archival tumour sample (except China).
8. Adequate organ function. Further inclusion criteria apply.
Exclusion criteria:
1. Serious concomitant disease or medical condition such as neurologic, psychiatric (including substance use disorder), active ulcers (gastrointestinal tract or skin) or laboratory abnormalities that may negatively impact patient safety during trial participation, affect compliance with trial requirements or invalidate assessments relevant for the investigation of the safety and preliminary efficacy of the investigational drugs.
2. Histologically or cytologically confirmed SCLC with combined histology, diagnosis of Merkel cell carcinoma, medullary thyroid carcinoma or neuroendocrine prostate cancer.
3. Presence of leptomeningeal disease and/or carcinomatous meningitis.
4. Known hypersensitivity to the trial drugs or their excipients, prior severe, life-threatening hypersensitivity reaction(s) to monoclonal antibodies, or significant risk of allergic or anaphylactic reaction(s) to any of the investigated drug products according to the investigator's judgement.
5. Participants who experienced severe, life-threatening immune-mediated adverse events, e.g. serious Grade 3 or higher immune-mediated adverse event (imAE) or infusion-related reactions, that led to permanent discontinuation while on treatment with immuno-oncology agents.
6. Persistent toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, asthenia/fatigue, amenorrhea/menstrual disorders, CTCAE Grade 2 peripheral neuropathy, and CTCAE Grade 2 endocrinopathies controlled by replacement therapy, and toxicities, which are considered irreversible but stable for at least 4 weeks, per investigator judgment).
7. Prior organ or tissue allograft.
8. History of or active interstitial lung disease, pulmonary fibrosis, organizing pneumonia or non-infectious pneumonitis (any grade) or any other condition resulting in significant impairment in lung function.
Further exclusion criteria apply.
ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer
This early-phase trial assigns patients with metastatic colorectal cancer to one of several biomarker-matched targeted or chemotherapy regimens (including anti-EGFR antibodies, BRAF/KRAS G12C inhibitors, HER2-directed agents, and cytotoxic combinations) based on individual tumor molecular characteristics to assess control of disease.
NCT07318389 · Phase 1 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Eligibility Criteria
* The participant has a histologically or cytologically confirmed diagnosis of colorectal cancer.
* Confirmation of non-MSI-H/pMMR status.
* Tumor that is measurable as per RECIST v1.1 and biopsy able, defined as lesion/tumor that can be biopsied without undue risk.
* Age ≥ 18 years.
* ECOG performance status 0-2.
* Due to the potential teratogenic effect of chemotherapy, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for an adequate amount of time following end of treatment based on the SOC indications for the administered regimen (Refer to Pregnancy Assessment Policy MD Anderson Institutional
Policy # CLN1114). This includes all female participants, between the onset of menses and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.
* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for an adequate amount of time following end of treatment based on the SOC indications for the administered regimen.
* The participant is willing and able to sign the informed consent in compliance with protocol requirements, including mandatory biopsies.
Exclusion Criteria
* Pregnancy.
* Participants with concurrent or recent (less than 1 year before consent) malignancies that have the potential to interfere with the study safety and/or endpoint assessments will be excluded.
* Participants for whom there is an intent to proceed to curative therapy (i.e., resection) will be excluded.
* Participants who have undergone treatment with both oxaliplatin and irinotecan in the metastatic setting will be excluded. Treatment with oxaliplatin in the adjuvant setting with relapse within 6 months will be counted as treatment in the metastatic setting for the purpose of this criterium.
* For participants who have undergone treatment for metastatic disease, participants who have not progressed (clinically or radiographically) on the most recent therapy will be excluded.
* Concurrent participation in any other interventional trial.
Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis
This phase III trial adds locoregional surgery, radiation, and metastasis-directed stereotactic body radiation therapy to standard HER2-targeted systemic therapy, versus systemic therapy alone, in patients with newly diagnosed oligometastatic/metastatic HER2-positive stage IV breast cancer.
NCT07578116 · Phase 3 · SWOG Cancer Research Network
Recruiting sites: Arkansas, Connecticut, Florida, Illinois, Iowa, Kansas, Mississippi, Missouri, Pennsylvania, Rhode Island, South Carolina, Tennessee, Virginia
Read full eligibility criteria
Inclusion Criteria:
* REGISTRATION STEP 1 - SCREENING \& INITIAL TREATMENT:
* Participants must have histologically confirmed de novo metastatic (i.e. American Joint Committee on Cancer \[AJCC\] stage IV, no prior history of breast cancer) HER2+ breast cancer with 1 to 5 distant metastatic lesions (oligometastatic). Metastatic breast cancer must be histologically confirmed through biopsy of a distant metastatic lesion unless it is not feasible or safe to biopsy a metastatic lesion, then there must be unequivocal evidence of metastasis on imaging and laboratory studies. HER2+ status must be confirmed in the breast tumor and distant metastatic site as defined per NCCN guidelines version 4.2025
* NOTE: If HER2 positivity at metastatic site is equivocal due to limitations in HER2 analysis in bone, or it is not feasible or safe to biopsy the metastatic lesion, then HER2 positivity based on breast tumor only is acceptable. If there is no breast lesion, HER2+ must be confirmed in at least one metastatic site
* Participants with brain metastases are eligible if they meet all of the following criteria at baseline:
* There are 5 or fewer intracranial lesions
* Each intracranial lesions is no larger than 2cm in longest dimension
* NOTE: The brain is counted as 1 distant site towards the oligometastatic definition. Brain imaging is not required for participants who have no neurological signs or symptoms suggestive of central nervous system (CNS) involvement; however, assessment of neurological symptoms and brain MRI is strongly encouraged to rule out CNS disease
* Participants must have no known leptomeningeal disease
* Participants must meet one of the following criteria prior to Step 1 registration:
* Treatment naïve and planning to initiate standard of care systemic HER2+ targeted treatment OR
* Have already initiated standard of care systemic HER2+ targeted treatment and have completed at least one (≥ 1) but no more than three (≤ 3) cycles prior to enrollment, without progression
* NOTE: Standard of care scans for baseline disease assessment must have been performed within 28 days prior to initiation of treatment
* Participants must not be receiving or planning to receive any investigational systemic therapy during study before disease progression
* Participants must not have received whole brain irradiation
* NOTE: Participants with up to five brain metastases may have received SRS/SRT either before or after initiation of systemic therapy. If lesions are small and asymptomatic and the participant is receiving CNS penetration they may be managed with observation
* Participants must be ≥ 18 years old at the time of registration
* Participants must have Zubrod performance status of 0-2
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* Participants must be able to safely receive the physician's choice of standard of care systemic HER2+ targeted treatment per the current Food and Drug Administration (FDA)-approved package insert(s), treating physician's discretion, and institutional guidelines
* Participants must be candidates for definitive surgical and radiotherapeutic management of locoregional disease opinion per the discretion of the treating physician
* Participants must be able to receive ablative dose stereotactic body radiation therapy (SBRT) to all metastatic lesions identified at baseline, in the opinion of the treating physician
* Participants must be offered the opportunity to participate in specimen banking
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and CIRB regulations
* REGISTRATION STEP 2 - COHORT ASSIGNMENT AND RANDOMIZATION:
* COHORT A: Participants must be registered to Step 2 within 14 days of staging scans performed after completing Step 1 systemic therapy
* COHORT A: Participants must have standard of care (SOC) staging scans and breast imaging performed following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
* COHORT A: Participants must have experienced partial or complete response in the breast (in the opinion of the treating physician) following 12-24 weeks of initial systemic therapy based on staging scans performed within 14 days prior to Step 2 registration
* Participants with breast lesion(s) at diagnosis must have a clinical response on breast imaging per the treating physician
* Metastatic lesions, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and bone response criteria, must have at least stable disease
* Brain metastases treated with SRS/SRT must have at least stable disease as per Response Assessment in Neuro-Oncology Brain Metastases (RANO BM) and must not require steroid treatment
* Participants with no known breast lesions at diagnosis must have at least partial response in the metastatic sites as assessed by RECIST and bone response criteria
* NOTE: The same imaging modality must be used as in Step 1
* COHORT A: Participants must be eligible for definitive surgical and radiotherapeutic management of locoregional disease per the discretion of the treating physician
* COHORT A: Participants must not have metastatic lesions that are not amenable to ablative dose stereotactic body radiation therapy (SBRT)
* Lung lesions that completely resolve after systemic therapy will not be targeted with SBRT, as it is not possible to achieve dose build-up
* The development of new sclerotic bone lesions after systemic therapy is not to be interpreted as disease progression, and all such lesions should be targeted with SBRT
* COHORT B: Participants must be registered to Step 2 within 14 days of staging scans performed after completing Step 1 systemic therapy
* COHORT B: Participants must have standard of care (SOC) staging and breast imaging performed following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
* COHORT B: Participants must experience clinically stable disease or progression following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
* Participants must have progression in metastatic lesions as assessed by RECIST and bone response criteria or may have stable disease in metastatic lesions by RECIST and bone response criteria if there is progression or no clinical response in the breast
* Participants with known breast lesion must have progression or no clinical response on breast imaging as per the treating physician
* NOTE: The same modality must be used as in Step 1
BL-M07D1 (Trastuzumab Brengitecan T-bren) vs Standard of Care Platinum-based Chemotherapy (PBC) for HER2-expressing Metastatic Urothelial Cancer After Progression on Anti-PD-(L)1-based Therapy
T-bren (trastuzumab brengitecan), a HER2-targeted antibody-drug conjugate, is being compared to platinum-based chemotherapy in HER2-expressing metastatic urothelial cancer after progression on anti-PD-(L)1 therapy.
NCT07869836 · Phase 3 · SystImmune Inc.
Recruiting sites: Georgia
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically documented metastatic or surgically unresectable transitional cell carcinoma (TCC) of the urothelium involving the renal pelvis, ureter, bladder, or urethra. Minor histologic variants (ie, \<50% overall) are acceptable, provided that TCC is the dominant histology.
* Disease progression or recurrence during or following anti-PD-(L)1-based therapy.
* Fresh biopsy or archival tumor samples.
* Documented HER2 expression by central laboratory testing.
* Eligible to receive carboplatin or cisplatin in combination with gemcitabine.
* At least 1 measurable lesion based on RECIST v1.1.
* An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
* Adequate organ function.
* Adequate coagulation parameters.
Exclusion Criteria:
* Prior topoisomerase inhibitor-based ADC therapy.
* Primary tumors in the central nervous system (CNS), active or untreated CNS metastases, or carcinomatous meningitis.
* Bladder cancers with small cell histology.
* Other prior or concurrent malignancies except for certain localized cancers or low-grade prostate cancer (if approved by sponsor), or other malignancy treated with curative intent with a disease-free interval of at least 3 years.
* Prior history of clinically significant bleeding, or perforation of the gastrointestinal tract within 6 months of randomization.
* Active autoimmune diseases and inflammatory diseases.
* History of noninfectious interstitial lung disease (ILD)/pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* Advanced/clinically significant lung disease (eg, poorly controlled chronic obstructive pulmonary disease or asthma, restrictive lung disease, or pulmonary hypertension) within 6 months prior to randomization.
* Known human immunodeficiency virus infection.
* Active hepatitis B virus (HBV) infection.
* Active hepatitis C virus (HCV) infection.
* Active or latent tuberculosis.
* Other protocol-specified inclusion/ exclusion criteria apply
Cemiplimab and Quad Shot Radiation for Cutaneous Squamous Cell Carcinoma in the Head and Neck
This trial tests cemiplimab, a PD-1 immune checkpoint inhibitor, combined with Quad Shot hypofractionated radiation therapy in frail/elderly patients with locally advanced, treatment-naive cutaneous squamous cell carcinoma of the head and neck.
NCT07869823 · Phase 1 · Vanderbilt-Ingram Cancer Center
Recruiting sites: Missouri
Read full eligibility criteria
Inclusion Criteria:
1. Locally advanced squamous cell carcinoma of the skin arising from the head and neck region.
2. Patients who have had prior treatment of a localized skin primary and now present with nodal recurrence or unresectable local recurrence are considered eligible as long as the recurrent disease has not been previously treated with radiation therapy
3. No prior systemic therapy including chemotherapy, targeted therapy or immunotherapy.
4. Deemed unfit for definitive curative intent treatment with surgery or radiation therapy due to one of the following criteria:
* ECOG Performance status 3 or 4;
* significant co-morbid medical conditions.
* frailty due to advanced age (must be \> 70 years of age if using this criterion only).
5. At least one measurable lesion as defined by RECIST 1.1.
6. Tumor tissue available for correlative-sequencing (tumor tissue from bony metastasis is not suitable; however, archival tissue is acceptable). A minimum of 6 cores from initial lymph node biopsy is strongly encouraged.
7. Adequate organ function as defined by:
• Absolute neutrophil count \>= 1,000/ul
* Platelets \>= 75,000/ul
* Hemoglobin \>= 7 g/dL (without requirement for transfusion in prior 4 weeks)
* Calculated serum creatinine clearance \> 20 mL/min by the Cockcroft-Gault formula (clearance \< 20mL/min will be allowed if patient is on a stable dialysis regimen)
* Total bilirubin =\< 1.5 X upper normal limit (UNL) (except subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl)
* Aspartate aminotransferase (AST) =\< 3.0 X UNL
* Alanine aminotransferase (ALT) =\< 3.0 X UN
8. Willing and able to sign informed consent.
9. Male or female ≥ 18 years of age at the time of informed consent.
10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and prior to receiving first dose of protocol-indicated treatment.
* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal.
* Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes.
* Women of childbearing potential must agree to use of contraceptives to prevent pregnancy.
Exclusion Criteria:
1. Prior systemic therapy for locally advanced cutaneous carcinoma of the head and neck (LACCHN)
2. Metastatic disease outside of the head and neck.
3. Prior treatment with checkpoint inhibitor therapy.
4. Planned re-irradiation: If disease is recurrent in a site previously treated with radiation, the patient will not be considered for study.
5. Active wound and/or infection overlaying the head or neck region that would prohibit safe radiation delivery.
6. Active second malignancy. Second malignancies that have been either cured or definitively treated and in remission are acceptable for inclusion.
7. Presence of cardiovascular disease, as defined by either:
\- New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication.
\- Transient ischemic attack or stroke within 1 year
8. Exclusions relating to infection or immunodeficiency including:
\- Any condition that requires ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
\- Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
Note: The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment.
\- Any infection requiring hospitalization or treatment with IV anti- infectives within 2 weeks of first dose of study medication
\- Uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent). Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
\- Prior recipient of organ transplantation.
9. Exclusions relating to vaccines including:
* Receipt of a live vaccine within 4 weeks of start of study medication
* Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
Exclusions relating to hypersensitivity including:
* Known hypersensitivity to the active substances or to any of the excipients.
Exclusions and information relating to pregnancy/contraception:
\- WOCBP\* and men\*\* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include:
1. Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
2. Intrauterine device; intrauterine hormone-releasing system;
3. Bilateral tubal occlusion/ligation;
4. Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or
5. Sexual abstinence Pregnancy testing and contraception are required for WOCBP. Pregnancy testing and contraception are not required for women who are postmenopausal or permanently sterile.
* WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women with documents hysterectomy or tubal ligation.
\*\*Male participants: A male participant will be excluded from the study if that participant does not agree to use condoms or practice sexual abstinence†‡, unless vasectomized, prior to the initial dose/start of study medication, during the study, and for at least 6 months after the last dose. Sperm donation is also prohibited during the same period. Vasectomy success must be confirmed by semen analysis.
Prohibited medications Participants must not receive live vaccines during the study. Participants using immunosuppressive doses (≥10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for physiologic corticosteroid replacement are not eligible for the study. Participants should not receive systemic corticosteroids such as hydrocortisone, prednisone, prednisolone (Solu-Medrol®) or dexamethasone (Decadron®) at any time throughout the study except as required premedication for chemotherapy or another study treatment per protocol and in the case of a life-threatening emergency and/or to treat an imAE.
Similarly, it is recommended that participants do not receive other immunosuppressive medications (eg, methotrexate) at any time throughout the study except in the case of a life-threatening emergency and/or to treat an imAE. Other immunosuppressive medications required to treat imAEs, IRRs, or life-threatening emergencies may be used at the investigator's discretion. Investigators are allowed to treat TEAEs requiring immunosuppressive medication per standard of care which may involve medications not specifically mentioned in the protocol.
Combination Therapy Using Durvalumab and Histotripsy for Treatment of Intrahepatic Cholangiocarcinoma
Histotripsy (non-thermal focused ultrasound tumor ablation using the Edison System) is combined with maintenance durvalumab (anti-PD-L1 monoclonal antibody) in patients with advanced intrahepatic cholangiocarcinoma who achieved disease control after first-line chemo-immunotherapy.
NCT07766187 · Phase 2 · University of Wisconsin, Madison
Recruiting sites: Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Participant diagnosed with histologically confirmed intrahepatic cholangiocarcinoma
* Participant demonstrates disease control following 18 weeks of chemotherapy (gemcitabine and/or cisplatin) and immunotherapy (durvalumab) as part of standard of care first line regimen.
* Participants are allowed to be on maintenance durvalumab therapy following disease control at 18 weeks prior to enrollment into the study.
* All participants must have prior biopsy confirming diagnosis of cholangiocarcinoma.
* Participant has iCCA tumor burden appropriate for biopsy and histotripsy treatment
* Participant able to undergo liver biopsy of Index Tumor.
* Index Tumor will be a predetermined non-histotripsy tumor in patients with multifocal disease, or a predetermined region of intentionally untreated tumor in patients with solitary disease.
* Participant to have iCCA deemed targetable for histotripsy.
* Participants with solitary tumor must have longest dimension ≥ 2.0 cm to allow for planned region of intentionally untreated Target Tumor for Index Tumor.
* Participants' iCCA is considered unresectable or patient is a non-surgical candidate
* Participant can undergo general anesthesia.
* Participant has a Child-Pugh Score of A or B (up to B8).
* Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening.
* Participant meets the following functional criteria, ≤7 days prior to the planned histotripsy procedure date
* Liver function: Alanine transaminase (ALT) and Aspartate transaminase (AST) \<2.5x upper limit of normal (ULN) and/or bilirubin \<2.5 ULN.
* Renal function: serum creatinine \<2x ULN.
* Hematologic function: Absolute neutrophil count \>1,000/uL and platelet \>50,000/uL, hemoglobin \>8.0 g/dL.
* Participant has an International Normalized Ratio (INR) score of \<3.0, ≤7 days prior to the planned histotripsy procedure date.
* Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to registration.
* Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for up to 14 months after the last dose of study drug(s). Males able to father a child must be willing to abstain from heterosexual vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for up to 11 months after the last dose of study drug(s).
* Ability of the participant to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
* Participant is pregnant or planning to become pregnant or nursing (lactating) during the trial period.
* Participant is enrolled in another investigational trial and/or is taking investigational medication or treated with an investigational device ≤30-days prior to planned histotripsy procedure date.
* In the Investigator's opinion, the subject has co-morbid disease(s) or condition(s) that would cause undue risk and preclude safe histotripsy treatment, including but not limited to interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis.
* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. .
* Participant has major surgical procedure or significant traumatic injury ≤2 weeks prior to the planned treatment or not fully recovered (CTCAE grade 1 or better) from side effects/complications of such procedure or trauma.
* Participant has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse effects (exceptions for alopecia, grade 2 neuropathy, grade 2 hypothyroidism, grade 2 hypoadrenalism) related to previous anti-cancer therapy. Please refer to inclusion criteria for lab-based enrollment parameters.
* Participant has a history of bleeding disorders (e.g. von Willebrand disease) or subject is suspected to have a bleeding disorder.
* Participant has uncorrectable coagulopathy.
* In the opinion of the Investigator, histotripsy is not a treatment option for the subject.
* Participant has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol.
* Participants' tumor(s) is not targetable per discretion of radiologist.
* Participant has a known sensitivity to contrast media and cannot be adequately pre-medicated.
* Participants' Target Tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation).
* History of solid organ or allogeneic bone marrow transplantation.
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
* Significant dementia or other mental condition that precludes the participant's ability to consent to the study.
* Untreated central nervous system (CNS) metastasis. Screening of asymptomatic patients for CNS metastasis is not required for enrollment.
* Live vaccine administration within 28 days of planned initial dose of durvalumab.
Concurrent Immunotherapy and Systemic Therapy With Stereotactic Body Radiation Therapy (SBRT) for Stage IV Cancers (COINSSS IV)
This phase II trial tests stereotactic body radiation therapy (SBRT) delivered to multiple metastatic lesions concurrently with standard-of-care immune checkpoint inhibitor therapy (pembrolizumab, nivolumab, atezolizumab, or ipilimumab) in first-line immunotherapy-based treatment of stage IV head & neck, non-small cell lung, cervical, esophageal, or gastric cancer.
NCT07770100 · Phase 2 · Mark Bernard
Recruiting sites: Kentucky
Read full eligibility criteria
Inclusion Criteria:
* Histologically proven advanced or stage IV head \& neck, non-small cell lung cancer, cervical, esophageal, gastric, and gastroesophageal cancer at least 6 metastases that are eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites with at least 1 other lesion meeting RECIST criteria of which this additional lesion not be treated with SBRT (biopsies performed for diagnosis are standard of care).
* At least 6 metastases eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites
* The 1 irradiated lesion must have a max point dose of 5Gy or less.
* Eligible for Immunotherapy for an FDA-approved indication as defined in section 6.1. NOTE: No limit is placed on prior systemic treatment unless it affects the eligibility for administration of immune checkpoint inhibitor therapy.
* If prior treatment with chemotherapy or radiotherapy or surgery has occurred: Prior chemotherapy or radiation must have concluded \> 21 days prior to the start of study treatment. Exception: study treatment can start within 2-3 days following GKS \[gamma knife surgery\] or whole brain radiation therapy \[ WBRT\], as long as patient is not experiencing ongoing/residual AE's related to GKS or WBRT at discretion of treating physician.
* First Line immunotherapy-based treatments only. The patient may have received prior cycles of immunotherapy, but has to be on the first line of immunotherapy-based treatments.
* If non-small cell lung cancer patient with pembrolizumab, PD-L1 testing CPS score \> or = to 50% will have to be shown
* If cervical cancer patient on secondary line therapy with pembrolizumab, CPS score of \> or = to 1 will have to be done. Please note, second line therapy with pembrolizumab is only allowed if the patient's first line of therapy did NOT include immunotherapy.
* If non-small cell lung cancer on first line ipilimumab in combination with nivolumab, PD-L1 of 1% and negative epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
* If pembrolizumab is given for a gastric cancer, a PD-L1 expression (CPS =1) will need to be shown
* If pembrolizumab is given as a single agent treatment after progression of one prior systemic therapy agent for esophageal or gastroesophageal squamous cell carcinoma histology, a PD-L1 (CPS=1) expression will have to be shown.
* ECOG Performance Status 0 - 1 (see Appendix A).
* Life expectancy \> or equal to 6 months.
* Adequate organ and bone marrow function prior to study treatment as defined by: Thresholds for lab values prior to initiation of study treatment.
* ANC \> or equal to 1,000/mm3
* Platelets \> or equal to 100,000/mm3
* Total bilirubin \< or equal to or equal to 1.5 x ULN
* AST and ALT - With hepatic metastasis, \< or equal to or equal to 5 x ULN. If no hepatic metastasis, \< or equal to 2.5 times x ULN
* Creatinine Or Creatinine Clearance \< or equal to 1.5 x ULNand/or CrCl \> or equal to 30ml/min (per 24-hour urine collection) or calculated according to the Cockcroft-Gault formula (Appendix B)
* No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for the past 3 years.
* Non-pregnant and non-nursing women -Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
* Women of childbearing potential and men must agree to use adequate contraception methods prescribed their the patients primary care physician, urologist, or obstetrician/gynecologist prior to study entry and for the duration of study participation.
* Subjects should use adequate birth control for at least 3 months after the last administration of immune checkpoint inhibitors.
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Presence of \< or equal to 5 sites amenable to SBRT
* Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor
* No more than 7 metastatic sites to an organ, defined as liver, left lung, right lung, single anatomically bone site (e.g. femur, humerus, single vertebral body).
NOTE: Multiple different vertebral bodies are allowed.
* Peritoneal involvement, at the discretion of the study PI. NOTE: Peritoneal metastasis does not exclude GI nor cervical cancer, except in cases where there is a separate focus of spread to the peritoneum.
* Presence of liver cirrhosis of any grade prohibits SBRT to the liver. NOTE: Pt can enroll to trial if receiving SBRT to other non-liver metastatic sites.
* A plan that cannot meet organ at risk tolerance (as defined in section 6.7.2.1) Auto-immune diagnosis Medications prohibited while receiving concurrent SBRT: gemcitabine, Adriamycin, VEGF or BRAF inhibitors.
NOTE: However, if the patient is on the prohibited agent(s), the patient is still eligible for the trial so long as the prohibited agent can safely be held for at least 1 month before starting SBRT, during SBRT, and 1 month after completion of SBRT.
-Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury (injury requiring immediate surgical intervention or involving loss of consciousness) within 14 days prior to registration or those patients who receive a nonCNS minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration.
NOTE: There is no waiting period for central line placement. There is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain.
* Active clinically serious infection \> CTCAE Grade 2.
* Serious non-healing wound, ulcer or bone fracture.
* Uncontrolled inter-current illness. This includes, but is not limited to: ongoing or active infection; symptomatic congestive heart failure (NYHA class III or IV); unstable angina pectoris or new onset angina that began within the last 3 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; thrombotic/ embolic events such as cerebrovascular accident, including transient ischemic attacks within the past 6 months;
* Uncontrolled hypertension defined as systolic blood pressure \>150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management; Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C; Known Grade 3 or 4 neurotoxicity.
* Receipt of live attenuated vaccine within 30 days prior to the first dose of ICI.
Note: Patients, if randomized, should not receive live vaccine while receiving ICI and up to 30 days after the last dose of ICI.
-Inclusion of Women and Minorities - Consistent with NIH policy, both men and women of all races and ethnic groups are eligible for this trial.
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
SX-682, an oral CXCR1/2 antagonist, is combined with docetaxel in recurrent/metastatic head and neck squamous cell carcinoma, salivary gland carcinoma, or advanced/metastatic castration-resistant prostate cancer.
NCT07667400 · Phase 1/2 · National Cancer Institute (NCI)
Recruiting sites: Maryland
Read full eligibility criteria
* INCLUSION CRITERIA:
All Participants
* Age \>= 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) \<= 2
* Participants must have adequate organ and marrow function as defined below:
* ANC \>= 1,500/mcL
* Hemoglobin (Hgb) \>= 9 g/dL
* Platelets (PLTs) \>= 100,000/mcL
* Creatinine clearance \>= 50 mL/min (by Cockroft-Gault formula)
* Total bilirubin \<= 1.5 x iULN (\<= 3 x ULN in participants with known/suspected Gilbert s disease)
* ALT/AST \<= 2.5 x iULN
* Activated partial thromboplastin time (aPTT) \<= 1.5 x iULN
* Contraception as follows:
* Women of child-bearing potential (WOCBP) must agree to use an effective method of contraception (barrier, hormonal, intrauterine device \[IUD\], surgical sterilization, abstinence) prior to study entry, for the duration of study treatment, and for up to 2 months after discontinuation of the study drugs. A participant may request a male partner to use an effective form of contraception to fulfill this requirement.
* Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 4 months after discontinuation of the study drugs. A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men able to father a child must not freeze or donate sperm within the same period.
* Nursing participants must be willing to discontinue nursing from study treatment initiation through one week after the last dose of study drugs.
* Participants must be able to swallow oral medications.
* Human immunodeficiency virus (HIV)-infected participants must have undetectable viral load (VL) and be on effective anti-retroviral therapy within 4 weeks prior to the study treatment initiation and have no history of opportunistic infections or Castleman s disease within 12 months prior to the study treatment initiation.
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV VL.
* Participants with evidence of chronic hepatitis C virus (HCV) infection must have undetectable HCV VL.
* Participants must be able to understand and willing to sign a written informed consent document.
Participants with HNC
* Histologically confirmed HNSCC (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses, nasopharynx) or SGC (including ACC and non-ACC) and recurrent/metastatic (R/M) or advanced incurable disease.
* Prior treatment as follows:
* Participants with R/M HNSCC must have prior systemic treatment (platinum-based chemotherapy and/or anti-PD(L)1 treatment).
* Participants with R/M SGC may have any number of prior systemic treatment lines; prior systemic treatment not required for participation.
* Participants must not have received systemic anticancer treatment within 3 weeks prior to first treatment administration. Note: Treatment-related toxicities must have resolved to Grade \<2 or be minimal and not constitute a safety risk. Participants with SGC previously treated with hormonal therapies (e.g., drugs targeting the androgen receptor) may continue these drugs concomitantly with study therapy. Participants with bone metastases or hypercalcemia on intravenous bisphosphonate medications, denosumab, or similar agents, are eligible to participate and may continue this treatment.
* Presence of \>= 1 measurable lesion by RECIST v 1.1 criteria.
Participants with mCRPC
* Documented histopathological confirmation of prostate cancer. If no pathologic report or specimen is available, participants may enroll with a history of clinical course consistent with the disease.
* Participants must have mCRPC, defined as at least one lesion on TC-99 bone scan or at least one lesion that is measurable per RECIST 1.1.
* Participants must need ADT as part of their cancer therapy (unless previous orchiectomy)
* Castrate testosterone level (\<50 ng/dl or 1.7 nmol/L)
* Prior treatment as follows:
* DTX for mCRPC is allowed but participants must not have had progression while on docetaxel or within 3 months after completing DTX for mCRPC
* Participants must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
* Progression defined as two consecutive rising PSA values at least 1 week apart or radiographic evidence of progression seen on computed tomography (CT) scan or TC- 99 bone scan.
* Toxicities related to prior therapy, including surgery and/or radiation, must have resolved to \< Grade 1 per CTCAE v.6.0.
EXCLUSION CRITERIA:
All participants
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to DTX, SX-682, or other agents used in study (e.g., polysorbate 80).
* Known active brain metastases. Note: Participants with previously treated brain metastases are eligible if imaging at least four weeks prior to first trial treatment shows no evidence of progression and neurologic symptoms have resolved, have no new or enlarging brain metastases, and are not using glucocorticoids for at least a week prior to first trial treatment
* Participants must not have received other investigational agents within 3 weeks prior to the first dose of the study drug(s).
* Participants must not have received major surgery within 14 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). If participant underwent major surgery, they must have recovered adequately (according to the Principal Investigator) from the toxicity and/or complications from the intervention prior to starting study treatment.
* Treatment (systemic) with any medications or substances that are moderate or strong inducers or moderate or strong inhibitors of cytochrome P450 (CYP3A4) listed at https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions- table-substrates-inhibitors-and-inducers#table2-2,table3-3,table5-2 within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of the study treatment.
* Prior or concurrent malignancy whose natural history or treatment has potential to interfere with the safety or efficacy assessment of the study treatment.
* Participants with serious uncontrolled intercurrent illness evaluated by medical history, electrocardiogram (EKG), and physical exam that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.
Participants with HNC
* Participants must not have received large-field radiotherapy within 2 weeks prior to first treatment administration. All residual treatment-related toxicities must have resolved to Grade \<2 (except for radiation-induced xerostomia/dysgeusia) or be minimal and not constitute a safety risk.
* Positive pregnancy serum or urine beta-human chorionic gonadotropin (beta-hCG) test
Participants with mCRPC
* Use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 1 week prior to the study treatment initiation.
* Cancer related neuropathy at screening
* Baseline QTcF \>= 470 ms
GI-102 (CD80-IgG4 Fc-IL2v3) in Combination With Pasritamig in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) (JET-201)
GI-102, a CD80-IgG4 Fc-IL2v fusion protein targeting CTLA-4/CD28 pathway with immunostimulatory activity, is studied in combination with pasritamig, a KLK2xCD3 bispecific T-cell engager, in metastatic castration-resistant prostate cancer progressing after prior novel hormonal therapy.
NCT07871435 · Phase 1/2 · GI Innovation, Inc.
Recruiting sites: New York
Read full eligibility criteria
Key Inclusion Criteria:
* Male participants aged ≥18 years (or ≥19 years according to local regulatory requirements).
* ECOG performance status of 0 to 1.
* Histologically confirmed advanced prostate adenocarcinoma with measurable or evaluable disease. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, primary small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma (or pathologic evidence of conversion to) is disallowed.
* Metastatic castration-resistant prostate cancer (mCRPC) with documented disease progression following at least one line of novel androgen receptor-targeted therapy.
* PSA ≥2 ng/mL at screening.
* No more than 2 prior taxane regimens and no prior cytotoxic chemotherapy other than taxane therapy.
* Prior orchiectomy or ongoing androgen deprivation therapy with castrate testosterone levels.
* Adequate organ and marrow function and adequate cardiovascular function.
* Adequate recovery from prior anticancer therapy-related adverse events.
* Willingness and ability to comply with study procedures and protocol-specified contraception requirements.
Key Exclusion Criteria:
* Active or prior CNS metastases, carcinomatous meningitis, or clinically unstable spinal cord compression.
* Significant uncontrolled cardiovascular, pulmonary, hepatic, autoimmune, infectious, or other systemic disease.
* Active or recent clinically significant infection, including active tuberculosis, hepatitis B, or hepatitis C.
* Active pneumonitis or interstitial lung disease (ILD), or history of clinically significant pneumonitis/ILD.
* Recent treatment with investigational products, prohibited immunomodulating agents, radiotherapy, major surgery, or other protocol-defined prohibited therapies.
* Prior treatment with CD3-directed therapies, including KLK2-CD3 bispecific antibodies or other CD3-targeting T-cell engagers.
* Known hypersensitivity to GI-102, pasritamig, or their excipients, or any other condition that may interfere with study participation or interpretation of results.
Osimertinib and Cyclosporine A to Enhance Antitumor Efficacy in NSCLC
This trial tests addition of cyclosporine A to the EGFR tyrosine kinase inhibitor osimertinib in ctDNA-positive, EGFR-mutant (exon 19 deletion or L858R) metastatic non-small cell lung cancer with persistent ctDNA shedding after osimertinib run-in.
NCT07874490 · Phase 2 · NYU Langone Health
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
* Age≥18 years, able to give informed consent.
* Standard of care (SOC) biopsy-proven metastatic non-small cell lung cancer, confirmed at NYU Langone Health (NYULH)
* Somatic activating mutation in EGFR exon 19 deletion or EGFR L858R in pre-treatment tumor biopsy or cytology from pleural fluid or cfDNA as detected by SOC testing.
* Either have not started a prior EGFR TKI therapy, or may have started osimertinib within 3 weeks of confirming eligibility and enrollment criteria of measurable disease per approval of PI, with no prior chemotherapy for treatment of metastatic disease (adjuvant therapy \> 6 months prior to study start is acceptable).
* Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per treating investigator. If a patient has already started on osimertinib there must be available pre-osimertinib baseline tumor assessments, to be utilized for RECIST 1.1 assessment.
* ECOG performance status of 0-2
* Adequate organ function
* Willing to use highly effective contraceptive measures if of child-bearing potential or if the patient's sexual partner is a woman of child-bearing potential
Exclusion Criteria:
* Pregnant or lactating women
* Any radiotherapy within 1 week prior to starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib. No washout window needed if the patients started on Osimertinib. They should continue on Osimertinib. If patients received radiation prior to Osimertinib, they should wait for 7 days from the last day of radiation to start Osimertinib. If patients are already on osimertinib at the time of initial consent and they happened to also have radiation prior to starting on osimertinib, they do not need a washout in order to meet eligibility criteria for the study.
* Any major surgery within 2 weeks of starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib.
* Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
* Currently receiving (or unable to stop prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial.
* Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the tablets or previous significant bowel resection that would preclude adequate absorption of Osimertinib or cyclosporine A.
* Mean resting corrected QT interval (QTcF) \> 470 msec
* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
* Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/Plasma potassium \<LLN, Serum/Plasma Magnesium \<LLN; Serum/Plasma Calcium \<LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes. If concomitant medication can not be discontinued, please notify and confirm with MSK PI prior to enrollment.
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
* History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
* History of hypersensitivity to active or inactive excipients of cyclosporine A or drugs with a similar chemical structure or class to cyclosporine A.
* History of autoimmune disease (excluding Hashimoto's thyroiditis).
Saruparib in Combination With Physician's Choice of ARPI in Patients With mHSPC Previously Treated With Docetaxel or 177Lu-PSMA Therapy Without Disease Progression and PSA ≥ 0.2 ng/mL (EvoPAR-PR05)
Saruparib, an oral PARP inhibitor, is being tested in combination with physician's choice ARPI (enzalutamide, darolutamide, or abiraterone) versus placebo plus ARPI in metastatic hormone-sensitive prostate cancer patients previously treated with docetaxel or 177Lu-PSMA therapy without disease progression.
NCT07711002 · Phase 3 · AstraZeneca
Recruiting sites: Arkansas, California, Florida, Hawaii, Illinois, Iowa, Maryland, Michigan, Minnesota, New Jersey, New Mexico, New York, Ohio, Oregon, South Carolina, South Dakota, Tennessee, Texas, Utah, Washington
Read full eligibility criteria
Inclusion Criteria:
* Participant must be ≥ 18 at the time of signing the informed consent.
* Histologically documented diagnosis of prostate adenocarcinoma that is de novo or recurrent and hormone-sensitive.
* Metastatic disease confirmed prior to initiation of previous treatment with docetaxel or Lu-PSMA-containing regimens for mHSPC.
* Previous treatment with docetaxel (IV, Q3w)- or Lu-PSMA (IV, Q6w) with last dose within past 6 months.
* Participants must have the following:
* Must be receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy.
* Had no evidence of disease progression
* Had all toxicities related to docetaxel- or Lu-PSMA-containing treatment (except for alopecia and peripheral neuropathy) resolved to CTCAE Grade 1 or lower.
* PSA ≥ 0.2 ng/mL within 14 days prior to randomization.
* Serum testosterone \< 1.7 nmol/L or 50 ng/dL.
* Palliative radiotherapy for symptoms management will be permitted and is to be completed at least 4 weeks prior to randomization for wide field radiation therapy and at least 2 weeks prior to randomization for limited field radiation therapy.
* Provision of a FFPE tumor tissue sample and a blood sample (for ctDNA).
* Confirmed HRRm, HRD and PTEN status.
* Adequate organ and bone marrow function.
* Minimum life expectancy of 6 months.
* Male, assigned at birth, inclusive of all gender identities.
* Contraceptive use by participants or participant partners should be consistent with local regulations.
* Capable of giving signed informed consent.
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Exclusion Criteria:
* Hypersensitivity to saruparib, ARPI or any excipients of these products or any contraindication or restriction based on the local label.
* Any history of persisting (\> 2 weeks) severe cytopenia due to any cause (eg, ANC\< 0.5 × 10\^9/L or platelets \< 50 × 10\^9/L)
* Any known predisposition to bleeding (eg, active peptic ulceration, recent \[within6 months\] hemorrhagic stroke, proliferative diabetic retinopathy.
* Spinal cord compression or brain metastases unless asymptomatic and stable.
* History of MDS/AML or with features suggestive of MDS/AML
* History of another primary malignancy, with some exceptions.
* Any chronic gastrointestinal diseases or conditions including inability to swallow the formulated product that would preclude adequate absorption of any study drug.
* History of seizure or predispose to seizure, including any history of loss of consciousness or transient ischemic attack within 12 months of enrolment.
* Serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
* Major surgical procedure or significant traumatic injury within 4 weeks of the first dose or an anticipated need for major surgery during the study.
* Switched ARPI agent in previous treatment for mHSPC due to disease progression. Note: if the ARPI agent was switched due to any reason other than disease progression and switch was prior to ICF signature, participants will be eligible.
* Any prior treatment with a PARPi or platinum chemotherapy.
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Treatment for Advanced Non-small Cell Lung Cancer With Actionable Genomic Alterations After Targeted Treatment and Chemotherapy (An Expanded Lung-MAP Treatment Trial)
This trial tests sacituzumab govitecan (a TROP2-directed antibody-drug conjugate), ivonescimab (a PD-1/VEGF bispecific antibody), or their combination in patients with recurrent/stage IV NSCLC harboring an actionable genomic alteration who progressed after targeted therapy and chemotherapy.
NCT07393555 · Phase 2 · SWOG Cancer Research Network
Recruiting sites: California, Georgia, Idaho, Illinois, Michigan, Missouri, Montana, New Hampshire, Ohio, Vermont, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Participants must have been assigned to S1900N by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900N is determined by submission of documentation of NSCLC harboring an actionable genomic alteration (AGA) in the LUNGMAP protocol. AGA is defined in this protocol as an activating driver alteration with an approved targeted therapy for lung cancer in one of the following genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1.
* Participants must have measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to randomization.
* Participants must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to randomization.
* Participants with spinal cord compression or brain metastases must not have residual neurological dysfunction, unless no further recovery is expected, and the participant has been stable on weaning doses of corticosteroids (≤ 10 mg daily prednisone or equivalent) prior to randomization. Participants with spinal cord compression or brain metastases that require local treatment must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to randomization.
* Participants must not have leptomeningeal disease that requires CNS-specific treatment prior to randomization and must not be planning to receive the CNS-specific treatment while on study.
* Participants must have progressed (in the opinion of the treating physician) during or following the most recent line of systemic therapy.
* Participants must have previously received an appropriate targeted therapy for the lung cancer AGA (ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1).
* Participants must have previously received platinum-based chemotherapy for stage IV or recurrent disease.
* Participants must have received no more than (\<=) 3 lines of prior cytotoxic therapy (including chemotherapy, antibody-drug conjugates) for NSCLC.
* Participants must not have received prior TROP2-targeted antibody-drug conjugate or a systemic therapy containing sacituzumab govitecan/SN-38.
* Participants must not have received prior anti-PD-1 or anti-PD-L1 antibody therapy.
* Participants must not have received any systemic lung cancer therapy (except orally administered drugs) within 21 days prior to randomization. Orally administered lung cancer therapies must not have been administered within 10 days prior to randomization.
* Participants must have completed any prior radiation therapy within 7 days prior to randomization.
* Participants must have recovered (≤ Grade 1) from any side effects of prior therapy (except for alopecia) prior to randomization.
* Participants must not be planning to receive any concurrent systemic therapy (e.g. chemotherapy, immunotherapy, targeted therapy etc) for lung cancer treatment while receiving treatment on this study.
* Participants' most recent Zubrod performance status must be 0-1 and be documented within 28 days prior to randomization.
* Participants must have a complete medical history and physical exam within 28 days prior to randomization.
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Hemoglobin \>= 10.0 g/dL (within 28 days prior to randomization)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to randomization). Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional ULN (within 28 days prior to randomization). Participants with history of liver metastasis must have AST and ALT ≤ 5 x ULN
* Participants must have calculated creatinine clearance ≥ 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to randomization.
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
* Participants must not have experienced an arterial or venous thrombotic event or hemoptysis within 28 days prior to randomization.
* Participants must not be planning to receive warfarin (or other coumadin derivatives) while receiving treatment on this study.
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization.
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization.
* Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
* Participants must be offered the opportunity to participate in specimen banking
Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors
177Lu-DFC413, a therapeutic radiopharmaceutical targeting an unelucidated tumor antigen (same target as the diagnostic 68Ga-NNS309) conjugated to lutetium-177, is being studied in patients with previously treated advanced/metastatic PDAC, NSCLC, HR+/HER2- or triple-negative breast cancer, colorectal cancer, and soft tissue sarcoma whose tumors show uptake on 68Ga-NNS309 imaging.
NCT07261631 · Phase 1 · Novartis Pharmaceuticals
Recruiting sites: New Jersey
Read full eligibility criteria
Inclusion Criteria:
* Adults ≥ 18 years with one of the following indications:
* Locally advanced unresectable or metastatic PDAC, with disease progression following, or intolerance to cytotoxic therapy, unless patient was ineligible to receive such therapy
* Locally advanced unresectable or metastatic NSCLC without any actionable genomic alterations with disease progression following, or intolerance to chemotherapy and immunotherapy, unless patient was ineligible to receive such therapy, or locally advanced unresectable or metastatic NSCLC with an actionable genomic alteration with disease progression following, or intolerance to chemotherapy and targeted therapy, unless patient was ineligible to receive such therapy
* Locally advanced unresectable or metastatic HR+/HER2- ductal and lobular breast cancer with disease progression following, or intolerance to, hormone therapy and CDK inhibitor, and at least one additional line of therapy, unless patient was ineligible to receive such therapy
* Locally advanced unresectable or metastatic triple negative breast cancer (TNBC) with disease progression following, or intolerance to, at least two lines of therapy, unless patient was ineligible to receive such therapy
* Locally advanced or metastatic unresectable CRC with disease progression following, or intolerance to cytotoxic chemotherapy, unless patient was ineligible to receive such therapy. Patients with known microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status must also have had disease progression following, or intolerance to, immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
* (Dose expansion only) Locally advanced unresectable or metastatic soft tissue sarcoma (excluding GIST and Kaposi) with disease progression following, or intolerance to, at least one line of systemic therapy
* Patients must have lesions showing 68Ga-NNS309 uptake
Exclusion Criteria:
* Absolute neutrophil count (ANC) \< 1.5 x 109/L, hemoglobin \< 9 g/dL, or platelet count \< 100 x 109/L
* QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
* eGFR \< 60 mL/min/1.73m2, calculated using CKD-EPI 2021 or measured
* Unmanageable urinary tract obstruction or urinary incontinence
* Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy
* Any prior radioligand therapy
* Radiation therapy within 4 weeks prior to the first dose of \[177Lu\]Lu-DFC413
Other protocol-defined inclusion/exclusion criteria may apply.
A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)
A DNAJB1-PRKACA fusion-targeted peptide vaccine combined with the glutamine antagonist DRP-104, plus the checkpoint inhibitors nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), is being studied in patients with advanced, metastatic or unresectable fibrolamellar hepatocellular carcinoma who have progressed on prior immunotherapy.
NCT07430202 · Phase 1 · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting sites: Maryland
Read full eligibility criteria
Inclusion Criteria:
* Must have histologically confirmed FLC that is metastatic or unresectable.
* Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.
* Must have demonstrated radiographic progression on prior or current immunotherapy.
* Age ≥ 12 years.
* Patients \< 18 years old must have a body weight ≥ 40 kg.
* ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
* Patients must have adequate kidney and liver function defined by study-specified laboratory tests.
* Must have measurable disease per RECIST 1.1
* Willingness to provide tissue and blood samples for mandatory translational research.
* Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
* For both Women and Men, must use acceptable form of birth control while on study.
* Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
* Patients with a history of prior treatment with checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies.
* Must have had chemotherapy or other systemic therapy or radiotherapy, as follows:
* Patients who have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
* Patients who have had surgery within 28 days of dosing of investigational agent, excluding minor procedures.
* Patients who have received other approved or investigational agents or device within 28 days of the first dose of study drug.
* Patients who have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered, with exception of grade 2 fatigue, rash, and endocrinopathy successfully managed hormone replacement therapy, or alopecia or stable neuropathy, unless approved by the IND Sponsor.
* Patients who have received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
* Known sensitivity to or history of allergic reactions attributed to compounds of similar chemical or biologic composition of polyinosinic-polycytidylic acid (Poly-ICLC) and/or DRP-104 and/or nivolumab and/or ipilimumab.
* History of severe hypersensitivity reaction to any monoclonal antibody.
* Has an active autoimmune disease.
* Prior allogeneic stem cell transplantation or organ transplantation.
* Has a diagnosis of immunodeficiency.
* Systemic corticosteroids at immunosuppressive doses.
* Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
* Has a pulse oximetry of \<92% on room air or is on supplemental home oxygen.
* Active or untreated brain metastases or leptomeningeal metastases.
* Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breastfeeding.
* Has a known history of Human Immunodeficiency Virus (HIV)/AIDS.
* Has active hepatitis B. Patients with chronic or acute HBV infection.
* Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.
* Unwilling or unable to follow the study schedule for any reason.
* Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
* Evidence of clinical ascites.
* Patients with QTc prolongation \> 470 ms according to Fridericia formula.
* Patients receiving potent inducers of CYP 3A4/5 (including but not limited to apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin and St. John's Wort) who cannot safely discontinue drug at least 14 days prior to Cycle 1 Day 1.
* Have had an allergen hyposensitization therapy within 2 weeks prior to initiation of study treatment.
A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer
This trial studies neoadjuvant tislelizumab (an anti-PD-1 antibody) combined with SX-682 (a CXCR1/2 inhibitor) in patients with newly diagnosed, surgically resectable pancreatic adenocarcinoma.
NCT05604560 · Phase 2 · Lei Zheng
Recruiting sites: Maryland, Texas
Read full eligibility criteria
Inclusion Criteria:
* Ability to understand and willingness to sign a written informed consent document.
* Age ≥18 years.
* Newly diagnosed have histologically or cytologically proven adenocarcinoma of the pancreas.
* Tumor must be resectable.
* Patient's acceptance to have a tumor biopsy.
* ECOG performance status 0 or 1
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
* For both Women and Men, must use acceptable form of birth control while on study.
Exclusion Criteria:
* Have received any anti-pancreatic cancer therapy.
* Have been diagnosed with another malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study.
* Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures
* Subjects with active, known or suspected autoimmune disease that may relapse.
* Systemic steroid therapy (\> 10mg daily prednisone equivalent) or immunosuppressive therapy within 14 days of first dose of study drug administration.
* Active infection requiring systemic therapy.
* Infection with HIV or hepatitis B or C at screening•
* History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, pulmonary embolism, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
* Prior allogeneic stem cell transplantation or organ transplantation
* Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug.
* Have received a live vaccine ≤ 28 days before first dose of study drug.
* Use of QT prolonging drugs within 2 weeks before the start of SX-682 dosing and for the length of the study.
* ECG demonstrating a QTc interval ≥ 470 msec or patients with congenital long QT syndrome.
* Severe hypersensitivity reaction to any monoclonal antibody.
* Concurrent participation in another therapeutic clinical study
* Pregnant or breastfeeding
A Study to Evaluate CRB-701 Compared to Investigator's Choice Therapy in Previously Treated Oropharyngeal Squamous Cell Carcinoma
CRB-701, a nectin-4-directed antibody-drug conjugate carrying MMAE, is being compared to investigator's choice chemotherapy (capecitabine, cetuximab, or docetaxel) in previously treated recurrent/metastatic oropharyngeal squamous cell carcinoma.
NCT07768189 · Phase 3 · Corbus Pharmaceuticals Inc.
Recruiting sites: Alabama, Arizona, California, Colorado, Connecticut, Delaware, Florida, Illinois, Iowa, Kentucky, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, New York, Ohio, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
* Histological and/or cytological confirmed diagnosis of OPSCC arising from tonsils, base of tongue, soft palate and posterior pharyngeal wall, with evidence of metastatic or recurrent disease not amenable to standard therapy with curative intent.
* Either second or third-line OPSCC patients who have progressed on or after receiving SOC therapy (that must have included platinum chemotherapy and an anti-PD-(L)1 antibody administered sequentially or together) OR received platinum chemotherapy and/or anti-PD-(L)1 therapy in the neoadjuvant or adjuvant setting or as part of definitive chemoradiation therapy, provided disease recurrence occurred less than 6 months after completion of the relevant systemic therapy.
* ECOG PS of 0-1
* Measurable disease as per RECIST v1.1, with at least one measurable lesion not previously irradiated unless unequivocal progression has been documented after radiation.
* Life expectancy of greater than 12 weeks at time of enrollment, as per Investigator's assessment.
Signed informed consent
Exclusion Criteria:
* Persistent CTCAE Grade \>1 clinically significant toxicities related to prior antineoplastic therapies, excluding alopecia.
* Significant active or chronic corneal disorders
* Pre-existing Grade ≥2 peripheral neuropathy
* Any other significant co-morbidities, disease, metabolic dysfunction, physical examination, or clinical laboratory finding that contraindicates the use of the investigational drug or may represent an unacceptable risk from treatment complications or may affect adherence to the study procedures or the interpretation of the results.
* Pregnant or breastfeeding females
Consolidative Metastasis and Primary Directed Therapy (MPDT) for Renal Cell Carcinoma (RCC)
This trial tests total consolidative metastasis- and primary-directed therapy (surgery, percutaneous cryoablation, and/or definitive radiotherapy) to enable systemic therapy discontinuation in patients with metastatic clear cell renal cell carcinoma who have had a partial response or stable disease after at least 6 months of immune checkpoint blockade-based therapy.
NCT06770855 · Phase N/A · Abramson Cancer Center at Penn Medicine
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of clear cell renal cell carcinoma (mixed histology acceptable but must have clear cell component)
* Metastatic clear cell RCC with 5 or fewer metastases at enrollment (excluding pulmonary nodules \<1.0cm)
* Stable disease or partial response as assessed by investigators following at least 6 months of immune checkpoint blockade-based therapy.
* Has disease amenable for total consolidative focal therapy (this will be determined by a multidisciplinary team which may include a combination of medical oncologists, urologists, interventional radiologists, and radiation oncologists).
* ECOG performance status \< 2
* Must have archival tissue (slide or Formalin-Fixed Paraffin-Embedded tissue) preceding prior systemic treatment for comparison to tissue from consolidation
* Consolidation surgery and biopsies are strongly encouraged to be within 42 days +/- 7 days of holding systemic therapy.
Exclusion Criteria:
* Subjects who have progressed during the first 6 months of immune checkpoint-blockade based therapy as determined by study investigator.
* Subjects who have a need for urgent focally directed therapy (i.e. symptomatic brain or spinal metastases). Stable spinal metastases resected and/or treated with SBRT in advance of or concurrently with immune checkpoint-blockade based therapy are allowed to participate.
* Any female of child-bearing potential who has a positive urine pregnancy test within 72 hours before screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive serum pregnancy test result.
Phase 1/2 Window Of Opportunity Study Of TROP2 CAR/IL-15 TGFBR2 KO NK Cells Delivered Intraperitoneally For The Management Of Gastric Cancer Metastatic To The Peritoneum
TROP2-targeted CAR/IL-15 TGFBR2-knockout NK cell therapy delivered intraperitoneally after lymphodepleting chemotherapy, studied in a Phase 1/2 trial for stage IV gastric/gastroesophageal junction adenocarcinoma metastatic to the peritoneum.
NCT07509008 · Phase 1/2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Subjects must be 18 years or older. Because no dosing or adverse event data are currently available on the use of CAR NK cells in combination with our standard of care approaches of cytoreductive surgery with intraperitoneal chemotherapy in patients \<18 years of age, children are excluded from this study.
2. Subjects must be willing and able to provide informed consent.
3. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. A female participant is eligible to participate if at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
2. A WOCBP who agrees to follow the contraceptive guidelines in Appendix 1 during the treatment period and for at least 3 months after the last dose of study treatment.
5. Subjects must have histology confirming diagnosis of adenocarcinoma of the stomach or gastroesophageal junction with pathology reviewed at MD Anderson Cancer Center.
6. Subjects must have histology confirming diagnosis of Stage IV adenocarcinoma of the stomach or gastroesophageal junction metastatic to the peritoneum based on either positive cytology (peritoneal washings/ascites) or peritoneal biopsy, with pathology reviewed at MD Anderson Cancer Center. Ovarian metastases are considered peritoneal metastases. Disease outside the peritoneal cavity is allowed as long as metastases are present within the peritoneal cavity.
7. Subjects must be at least 4 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy. Zolbetuximab may be continued during the peritoneal-directed treatment and NK cell therapy.
8. Subjects must be willing and able to undergo a minimally invasive staging cytoreductive surgery with intraperitoneal port placement and scheduled peritoneal fluid and peripheral blood draws.
9. Subjects must have adequate organ function as defined in the following table (Table 1).
Specimens must be collected within 10 days prior to the start of study treatment.
Exclusion Criteria:
1. Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 3 months after the last dose of trial treatment. WOCBP must have a negative serum pregnancy test within 72 hours of admission prior to lymphodepleting chemotherapy (see Appendix 1).
2. Has received systemic anti-cancer therapy including investigational agents within 4 weeks of starting lymphodepleting chemotherapy.
3. If a participant received previous systemic or targeted therapy, immunotherapy, or major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. In patients receiving standard of care zolbetuximab, this therapy may be continued.
4. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
5. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
6. Is currently receiving another investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
7. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
9. Active autoimmune disease that has required systemic treatment in the past 2 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
10. History of interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
11. Serious active infection, as determined by Principal Investigator or treating physician, requiring intravenous systemic therapy.
12. Known history of uncontrolled Human Immunodeficiency Virus (HIV) infection. Patients with HIV infection and undetectable viral load may participate.
13. Known history of chronic Hepatitis B or Hepatitis C virus infection.
14. Known history of active TB (Bacillus Tuberculosis).
15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
16. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
17. Has had an allogenic tissue/solid organ transplant.
18. Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular event, or cardiac arrhythmia associated with hemodynamic instability. Note: medically controlled arrhythmia would be permitted.
19. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. Subject with known deep vein thrombosis/pulmonary embolism that are under appropriate anti-coagulation treatment are eligible.
20. Radiographic distribution of disease that in the investigator's opinion would impart excessive risk to participation in this protocol.
21. Active peritonitis or diverticulitis.
22. Medical or surgical history that in the treating physician's opinion would make the subject not a suitable candidate for intraperitoneal therapy. Examples would include surgically documentedextensive intraperitoneal adhesions or large volume ascites.
23. History of severe hypersensitivity reaction with biologic therapy (e.g. monoclonal antibodies)
Study of Izalontamab Brengitecan (BMS-986507) in Combination With Osimertinib Versus Osimertinib Monotherapy or Osimertinib in Combination With Platinum-based Chemotherapy for EGFRmt Non-small Cell Lung Cancer (IZABRIGHT-Lung02)
Izalontamab brengitecan (iza-bren), an agent whose mechanism is not stated in the registry, is studied in combination with osimertinib versus osimertinib alone or osimertinib plus platinum-based chemotherapy as first-line treatment for previously untreated EGFR-mutant locally advanced or metastatic non-small cell lung cancer.
NCT07680790 · Phase 3 · Bristol-Myers Squibb
Recruiting sites: California, Colorado, Florida, Illinois, Maryland, Minnesota, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, West Virginia
Read full eligibility criteria
Inclusion Criteria:
* Participants must have histologically or cytologically confirmed non-squamous NSCLC, newly diagnosed locally advanced (Stage IIIB/IIIC), metastatic (Stage IVA/IVB), or recurrent disease not amenable to curative surgery or definitive radiotherapy and requiring systemic treatment
* Participants must have documented EGFR-TKI-sensitizing mutation (exon 19 deletion or exon 21 L858R substitution)
* Participants must have measurable extracranial disease per RECIST v1.1 as assessed by the investigator
* Participants must have ECOG Performance Status 0-1
Exclusion Criteria:
* Participants must not have unstable, symptomatic, or uncontrolled CNS metastases, including brain, leptomeningeal disease, and/or spinal cord compression
* Participants must not have history of ILD/pneumonitis requiring treatment with steroids (≥ Grade 2), or current or suspected ILD/pneumonitis
* Participants must not have clinically significant cardiac disease
* Other protocol-defined inclusion/exclusion criteria apply.
Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metastatic Colorectal Cancer (LiGeR-CRC2)
Petosemtamab, a bispecific antibody targeting EGFR and LGR5, is being evaluated in combination with chemotherapy versus cetuximab or bevacizumab plus chemotherapy in RAS/BRAF wild-type, recurrent, unresectable or metastatic colorectal cancer after up to one prior line of therapy.
NCT07775287 · Phase 3 · Genmab
Recruiting sites: California, Georgia, Washington
Read full eligibility criteria
Key Inclusion Criteria:
* Histologically or cytologically confirmed colorectal adenocarcinoma that is recurrent, unresectable or metastatic.
* Must have documented KRAS and NRAS wt CRC, as determined by medical record of results from local testing or as assessed by central testing. Next-generation sequencing-based test results from tumor tissue are required for determining eligibility. At a minimum, local testing must have assessed the mutational status of KRAS and NRAS G12/G13, A59, Q61, K117, and A146 codons.
* Has received no more than 1 line of prior systemic therapy for unresectable or metastatic CRC, with documented disease progression. First line (1L) regimen must be fluoropyrimidine- and oxaliplatin- (if 2L choice of backbone is FOLFIRI) or irinotecan- (if 2L choice of backbone is fluorouracil + leucovorin (calcium folinate) + oxaliplatin \[FOLFOX\]) based. Prior anti-vascular endothelial growth factor receptor (VEGF) treatment is allowed.
* Must be eligible for treatment with mFOLFOX6 (if assigned by the investigator to receive mFOLFOX6) or FOLFIRI (if assigned by the investigator to receive FOLFIRI) according to local regulatory approvals and standard of care (SOC) guidelines.
Key Exclusion Criteria:
* BRAF V600 mutation (eg, V600E) and/or microsatellite instability-high/deficient mismatch repair tumor status and/or ERBB2/human epidermal growth factor receptor 2 (HER2) positive/amplified tumor status as documented by local test results in the medical record or from central testing or known documented activating HRAS mutation identified prior to enrollment from local testing results in the medical record, if available .
* Prior exposure to any agents that target epidermal growth factor receptor (EGFR) (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy).
* Prior exposure to irinotecan (for participants assigned to FOLFIRI) or oxaliplatin (for participants assigned to FOLFOX) in the metastatic setting.
* Known complete dihydropyrimidine dehydrogenase (DPD) deficiency or known homozygous/compound heterozygous dihydropyrimidine dehydrogenase gene (DPYD) variants associated with complete loss of DPD activity. Testing for DPD deficiency should be performed per local guidelines.
* For a participant who is to receive FOLFIRI: known to be homozygous for the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)\*28 or \*6 alleles or compound or double heterozygous for the UGT1A1\*28 and \*6 alleles. Testing for UGT1A1 should be done in accordance with local guidelines.
* Participants with non-colorectal adenocarcinumatous disease.
Note: Other protocol-defined Inclusion and Exclusion criteria may apply.
Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.
RYZ101 (225Ac-DOTATATE), a somatostatin receptor-targeted alpha-emitting radioconjugate, is studied alone or with endocrine therapy in SSTR-expressing ER+, HER2-negative unresectable or metastatic breast cancer.
NCT06590857 · Phase 1/2 · RayzeBio, Inc.
Recruiting sites: Arizona, California, Colorado, Florida, Georgia, Indiana, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, New Mexico, New York, Ohio, Pennsylvania, Texas, Utah, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria
Subjects must meet all the following criteria for enrollment in the study:
* Histologically confirmed, ER+, HER2-negative, locally advanced and unresectable or metastatic breast cancer not amenable to treatment with curative intent.
* Adequate renal, hematologic, and hepatic function
* Additional inclusion criteria for Monotherapy arm:
* Measurable disease with at least 80% SSTR-positive lesions by SSTR-PET imaging
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Documented radiologic progression after at least 2 and no more than 4 prior chemotherapy or ADC regimens in the metastatic setting
* Additional inclusion criteria for ET Combination arms:
* Prior treatment with CDK4/6 inhibitors in combination with endocrine therapy in the advanced or metastatic setting.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Bone only or bone dominant disease. At least 1 bone lesion must be SSTR-positive on SSTR-PET imaging. For bone dominant disease, at least 50% of soft tissue measurable lesions must be SSTR-positive on SSTR-PET imaging. At least one bone lesion must be positive on both SSTR-PET and on FDG-PET imaging
* Brain metastases are allowed if definitively treated and clinically stable as confirmed by interval imaging
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from the study:
* Prior radiopharmaceutical therapy, including radioembolization.
* Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1, except for alopecia.
* Significant cardiovascular disease
* Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, spinal cord compression, or leptomeningeal disease.
* History of hypersensitivity or allergy to 225Ac, 68Ga, 64Cu, octreotate, or any of the excipients of DOTATATE imaging agents.
* Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the study safety or efficacy assessments.
* Pregnancy or breastfeeding
* Additional exclusion criteria for ET Combination arms:
* Presence of liver metastases or symptomatic metastatic visceral disease
* Prior PARPi exposure or are candidates for PARPi per local guidelines
A Study to Investigate Mocertatug Rezetecan Compared With Chemotherapy in Participants With Endometrial Cancer After Platinum-based Chemotherapy and Immunotherapy (BEHOLD-Endometrial01)
Mocertatug rezetecan, a B7-H4-directed antibody-drug conjugate carrying a topoisomerase-1 inhibitor payload, is being compared with chemotherapy (paclitaxel or doxorubicin) in endometrial cancer patients who progressed after prior platinum-based chemotherapy and immunotherapy.
NCT07286331 · Phase 3 · GlaxoSmithKline
Recruiting sites: Alabama, Nebraska
Read full eligibility criteria
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
* Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF).
* Has histologically confirmed endometrial carcinoma including but not limited to endometroid, serous, clear cell, and endometrial carcinosarcoma. Mixed epithelial carcinomas are permitted.
* Has undergone at least 1 and no more than 2 lines of prior systemic treatment for EC. Up to 3 lines of prior systemic treatment are acceptable if one line was administered in the adjuvant/neo-adjuvant setting. The definition of prior lines of therapy is as follows:
* Adjuvant ± neo-adjuvant therapy counts as one line of treatment.
* Maintenance therapy is considered part of the preceding line and does not count as an independent line.
* Switching to another agent within the same class due to toxicity (without disease progression) is considered part of the same line of therapy.
* Unplanned addition or switching to a new anti-cancer therapy in a different class is considered a separate line of therapy.
* Hormonal therapy is NOT counted as a separate line.
* Must have progressed on or after prior platinum-based chemotherapy and have received anti- Programmed cell death 1 (PD-1) /anti- Programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination. Participants deemed unsuitable for a prior PD-1/PD-L1 inhibitor therapy (contraindications such as immunodeficiency, autoimmune disease that required systemic treatment) as determined by the investigator or treating physician are eligible.
* Participants must have a platinum-free interval of less than 12 months if they previously received platinum-based therapy solely in the adjuvant setting. The platinum-free interval is defined as the date of the last dose of platinum-based chemotherapy to the date of disease progression.
* If PD-L1/PD-1 inhibitor therapy was administered with platinum-based treatment, participant is eligible regardless of whether the Platinum-free interval (PFI) exceeds 12 months.
* Participants with metastatic disease who underwent treatment including gynecological surgery followed by a platinum-based regimen, or those deemed intolerant to platinum-based therapy, are eligible regardless of whether the PFI exceeds 12 months.
* Has provided a Formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression, with the result of B7-H4 expression testing available prior to date of randomization.
* Has ≥1 Target Lesion per RECIST 1.1 by BICR eligibility review of screening scans.
* Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
* Is a Participant of non-childbearing potential (PONCBP) OR
* Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, 30 days prior to Cycle 1 Day 1 (C1D1) and during the study intervention period and for at least 8 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
* A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention
* If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Additional requirements for pregnancy testing during and after study intervention are described in protocol.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy.
* Is capable of giving signed informed consent including compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Has adequate organ function.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Mesenchymal tumors of the uterus (uterine sarcomas) and neuroendocrine uterine cancer.
* Has a malignancy (except disease under study) that has progressed or required active treatment within the past 36 months prior to date of randomization except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of metastatic disease, or that is otherwise considered cured by the investigator.
* Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
* Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases). Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥14 days before date of C1D1 are not excluded from participation.
* Has any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
* Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤ Grade 1 or to the baseline status preceding prior therapy, excluding alopecia, hearing loss, vitiligo and endocrinopathy managed with replacement therapy, or that the investigator, with the agreement of the sponsor, considers to be stable or not clinically relevant for the tolerability of study intervention in the current clinical study.
* Has any serious and/or unstable medical condition (including infection) or any serious and/or unstable psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
* Has had any major surgery within 28 days prior to date of C1D1 or history of local radiotherapy within 21 days prior to C1D1.
* Has received treatment with an investigational agent within 30 days prior to C1D1.
* Has received prior therapy with Topo1i (e.g. irinotecan or topotecan) or ADC with a Topo1i payload, or B7-H4 targeted therapy.
* Has received treatment with any cytotoxic chemotherapy drugs or other antitumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy and investigational drug) within 30 days or 5 half-lives, whichever is shorter, prior to C1D1; or need to continue these drugs during the study.
* Has received any live vaccine within 30 days prior to C1D1.Note: mRNA and adenoviral-based Coronavirus disease 2019 (COVID-19) vaccines are considered non-live.
* Has received treatment with inhibitors of P-glycoprotein (P-gp), Breast cancer resistant protein (BCRP), or OATP1B1/1B3 transporters within 7 days prior to first dose of study drug. P-gp inducers should be discontinued for at least 14 days before the start of the study drug.
* Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte colony stimulating factor (G-CSF), Granulocyte-macrophage colony stimulating factor (GM-CSF), or recombinant erythropoietin) within 14 days prior to C1D1.
* Has a known Human immunodeficiency virus (HIV) infection AND meets at least 1 of the following criteria:
* Has documented evidence of plasma HIV-1 Ribonucleic acid (RNA) ≥50 c/mL within 3 months prior to or at screening. In the 3 to 12 months prior to screening, plasma HIV1 RNA levels consistently \<50 c/mL are required for enrollment; if multiple instances of plasma HIV-1 RNA values ≥50 c/mL occurred in the 3 to 12 months prior to screening, the participant is not eligible for enrollment unless, per the investigator's assessment, the elevations were neither persistent nor associated with antiretroviral resistance; OR
* Has not had Cluster of differentiation (CD)4 cell counts measured in the past 12 months (i.e., at least 2 separate measurements taken a minimum of 28 days apart, 1 of which must be conducted at screening); OR
* Has had any CD4 cell count values ≤350 cells/mm3 in the past 12 months. OR
* Has had 1 or more changes in their combination antiretroviral therapy regimen or has received an antiretroviral therapy regimen that is inconsistent with locally recommended guidelines during the 3 months prior to screening; OR
* Has a history of HIV-associated non-Hodgkin lymphoma within 5 years prior to screening or a history of HIV-associated invasive cervical cancer; OR
* Has received treatment with an HIV1 immunotherapeutic vaccine within 90 days prior to screening.
* Has an Alanine aminotransferase (ALT) value \>2.5× Upper limit of normal (ULN) and/or for participants documented liver metastases/tumor infiltration has an ALT value \>5x ULN
* Has a total bilirubin value \>1.5x ULN.
* Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
* Has documented presence of Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb) at screening unless they meet both the following criteria:
* Participants with chronic Hepatitis B virus (HBV) infection (HBsAg+) or positive HBcAb are required to be receiving effective antiviral therapy (i.e., with nucleos(t)ide analogs \[Tenofovir or Entecavir\]) for at least 14 days prior to C1D1 and are willing to continue for at least 6 months after treatment discontinuation or longer at the discretion of the treating hepatologist.
* HBV Deoxyribonucleic acid (DNA) must be adequately suppressed, as per institutional or local guidelines, prior to initiation of study intervention.
* Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to C1D1 unless HCV RNA is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment.
* Has a positive HCV RNA test result at screening or within 3 months prior to C1D1.
* Has QTc \>470 milliseconds (msec)
* Has a history within 12 months prior to screening of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure \[NYHA 1994\], or clinically significant arrhythmia not controlled by standard of care therapy.
* Has Left ventricular ejection fraction (LVEF) \<50% or less than institutional lower limit of normal.
* Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).
A Phase 1, First-in-Human (FIH), Open-Label, Dose-Escalation and Dose Expansion Study of the Peptide Drug Conjugate (PDC), TS-104, as a Monotherapy in Subjects With Select Advanced Solid Tumors
TS-104 is a peptide-drug conjugate that uses an integrin-binding targeting peptide to deliver the cytotoxic MMAE, studied as monotherapy in a first-in-human dose-escalation/expansion trial for advanced NSCLC, HNSCC, esophageal, gastric, endometrial, and ovarian cancers.
NCT07814248 · Phase 1 · TwoStep Therapeutics, Inc.
Recruiting sites: Ohio, Oregon, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Males \& females ≥18 years of age at the time of consent
* Willingness to provide written informed consent, according to local guidelines.
* Subjects who have histologically or cytologically documented, unresectable locally advanced, or metastatic solid malignancy that is progressing or has failed the minimum therapies listed below or who are intolerant of, ineligible for, or refuse standard of care (SOC) therapy according to local guidelines:
1. Non-small cell lung cancer (NSCLC)
2. Head and neck squamous cell carcinoma (HNSCC)
3. Esophageal cancer
4. Endometrial cancer
5. Ovarian cancer
6. Gastric cancer
* Subjects must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* All subjects must have tumor tissue available for retrospective analysis
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate organ function as defined by the following criteria:
1. AST and ALT ≤2.5×ULN or ≤5×ULN for subjects with liver metastases
2. Total serum bilirubin ≤1.5×ULN except in the presence of Gilbert's Syndrome where direct bilirubin should be ≤ULN
3. ANC ≥1.5×109/L
4. Platelets ≥100×109/L without transfusion support within 14 days prior to study treatment
5. Hemoglobin ≥9.0 g/dL without transfusion support within 14 days prior to study treatment
6. Calculated creatinine clearance ≥60 mL/min by Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
7. Coagulation tests ≤1.5×ULN unless subject is receiving anticoagulant therapy, as long as prothrombin time (PT), International Normalized Ratio (INR), or activated partial thromboplastin time (aPTT) is within the therapeutic range of intended use of anticoagulants
* Negative serum pregnancy test for women of childbearing potential (WOCBP) at Screening and willingness to use highly effective contraception for the duration of the trial and for 6 months following the last dose of TS-104
* Male subjects must agree to use a highly effective method of contraception while on study and for 6 months following the last dose of TS-104
Exclusion Criteria:
* Unresolved toxicity higher than Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v 6.0 (or higher) attributed to any prior therapy/procedure at Screening, except for alopecia, well-controlled Grade 2 hypothyroidism, or Grade 2 adrenal insufficiency that is actively managed with appropriate therapy
* Subjects with ongoing sensory or motor neuropathy ≥Grade 2
* Subjects with active or chronic keratitis or corneal disorders, including ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the Investigator.
* Known sensitivity to any of the ingredients of TS-104 or MMAE
* Prior treatment with tubulin-inhibitor-based drug conjugates, including antibody-drug conjugates (ADCs) with tubulin inhibitor payloads, ie, Emrelis (MMAE payload) for c-Met-high NSCLC or Elahere (DM4 payload) for FRα-high ovarian cancer. For clarity, prior treatment with standard taxane-based chemotherapy (eg, paclitaxel) is permitted.
* Subjects currently receiving cancer therapy (ie, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery, and/or tumor embolization) or expected to require any other form of antineoplastic therapy while on study.
* Subject with history of other malignancy other than the one for which they participate in the study (exceptions include definitively resected basal cell carcinoma and other in situ cancers) - unless the subject has undergone curative therapy with no evidence of that disease for 3 years
* Major surgery or planned major surgery (excluding placement of vascular access device) within 4 weeks of Cycle 1 Day 1 (C1D1)
* Subjects who are currently pregnant or breastfeeding
* Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, uncontrolled diabetes mellitus, active or chronic bleeding event within 28 days prior to C1D1, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician. This includes any preexisting medical history that could impair the proper assessment of the study results (eg, severe pulmonary function compromise unrelated to underlying malignancy).
* ≥Grade 3 pulmonary disease unrelated to underlying malignancy
* History of noninfectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at Screening or the presence of residual symptoms
* Clinically significant, uncontrolled cardiovascular disease including: myocardial infarction or unstable angina within the last 6 months, symptomatic congestive heart failure (New York Heart Association Classification \>Class II), or serious uncontrolled cardiac arrhythmia within the last 6 months of Screening
* History of long QT syndrome or subject whose corrected QT interval measured by Fridericia's method at Screening is prolonged (\>470 msec)
* Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite optimal medical management
* Current treatment with strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 or inhibitors of P-glycoprotein (P-gp) including herbal or food based
* Known active central nervous system metastases.
A Study of Patritumab Deruxtecan (HER3-DXd) in Combination With Trastuzumab Deruxtecan (T-DXd) in Participants With HR-Positive, HER2-Low or HER2-Ultralow Unresectable or Metastatic Breast Cancer
This trial tests the combination of patritumab deruxtecan (a HER3-targeted antibody-drug conjugate) with trastuzumab deruxtecan (a HER2-targeted antibody-drug conjugate) in patients with hormone receptor-positive, HER2-low or HER2-ultralow, unresectable or metastatic breast cancer refractory to endocrine therapy.
NCT07701941 · Phase 1/2 · Daiichi Sankyo
Recruiting sites: California, Colorado, Connecticut, Massachusetts, New York, Oregon, Tennessee, Texas, Virginia
Read full eligibility criteria
Key Inclusion Criteria:
1. Pathologically documented breast cancer that meets the following:
1. Unresectable or metastatic.
2. HR+ based on testing performed locally. HR+ (estrogen receptor \[ER\] and/or progesterone receptor \[PgR\] positive \[ER or PgR greater than equal to (≥)1 percent (%)\] per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] 2020 guidelines) in the unresectable or metastatic setting.
3. Assessed as HER2-low (defined as Immunohistochemistry (IHC)2+/In-situ hybridization (ISH)- or IHC1+) or HER2-ultralow (defined as IHC 0 with any membrane staining in greater than (\>) 0 and lesser than equal to (≤)10% of the cancer cells) locally for Part 1 and centrally for Part 2. The HER2 result must be from a tumor sample obtained in the unresectable or metastatic setting.
* For Dose Regimen Determination (Part 1), HER2 status used for eligibility assessment must be determined locally (according to applicable regulations) using the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc.). Additional HER2 testing will be performed locally and according to applicable regulations using the prescribed test during Screening only if prior results obtained with this test are not available for eligibility assessment.
* For Dose Expansion (Part 2), HER2 testing will be performed prospectively at a central laboratory using the pretreatment tumor tissue sample.
2. Provides a pretreatment tumor tissue sample that meets one of the following collection requirements:
1. Tissue biopsy collected from ≥1 lesion not previously irradiated and performed since progression with the most recent systemic cancer therapy regimen and prior to signature of the Tissue Screening informed consent form (ICF) (ARCHIVAL PRETREATMENT sample).
OR
2. Newly obtained pretreatment tumor biopsy from ≥1 lesion not previously irradiated and amenable to sampling, after signature of the Tissue Screening ICF (FRESH PRETREATMENT sample).
3. Documented radiologic disease progression as per investigator assessment per RECIST v1.1 criteria (during or after most recent treatment).
4. Documented refractoriness to endocrine therapy, defined as disease progression on one or more line of endocrine therapy in the unresectable or metastatic setting and determined by the investigator that participant would no longer benefit from further treatment with endocrine therapy.
5. Prior treatment with a Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in any setting. Subsequent endocrine therapies administered after progression on CDK4/6 inhibitor are allowed.
6. Participants with genomic alterations/mutations (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), phosphatase and tensin homolog (PTEN), AKT, or Breast Cancer gene (BRCA)1/2) who are eligible for approved targeted therapies in combination with endocrine therapy or as monotherapy (according to local label and availability) must have received the corresponding therapy prior to enrollment, unless contraindicated or not accessible in their country/region.
7. No prior chemotherapy for unresectable or metastatic breast cancer. Participants who have received chemotherapy in the neoadjuvant or adjuvant setting are eligible.
8. ECOG performance status 0 or 1 at the time of Screening.
9. Has ≥1 measurable lesion on CT or MRI per RECIST v1.1 by investigator assessment.
10. Has adequate bone marrow reserve and organ function based on local laboratory data within 7 days prior to the first dose as specified in the protocol.
Key Exclusion Criteria:
1. Prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of a topoisomerase I inhibitor (e.g., T-DXd) or any other topoisomerase I inhibitor therapy.
2. Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as CPFE, and any radiographic features consistent with ILA, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids.
3. Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the trial.
4. Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive or treated brain metastases who are asymptomatic (i.e., without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the trial but must have a stable neurologic status for ≥4 weeks prior to Cycle 1 Day 1. Participants with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis can enroll.
5. Inadequate washout period of prior treatment before randomization:
1. Whole brain radiation therapy less than (\<)28 days.
2. Monoclonal antibodies other than immune checkpoint inhibitors, such as anti-vascular endothelial growth factor (VEGF) (e.g., bevacizumab) and anti-epidermal growth factor receptor (EGFR) (e.g., cetuximab) \< 28 days.
3. Immune checkpoint inhibitor therapy \<21 days.
4. Major surgery (excluding placement of vascular access) \<28 days.
5. Radiotherapy treatment to more than 30% of the bone marrow or wide field radiation or palliative stereotactic radiation to chest \<28 days or palliative stereotactic radiation therapy to other anatomic areas \<14 days.
6. Chloroquine or hydroxychloroquine ≤14 days.
7. Hormonal therapy \<21 days prior to first dose of HER3-DXd.
8. Live or live attenuated virus vaccination \<30 days.
6. Uncontrolled or significant cardiovascular disease, including any of the following:
1. QTcF prolongation interval \>450 milliseconds (ms) (average of triplicate determinations at screening).
2. Left ventricular ejection fraction (LVEF) ≤50%.
3. Resting systolic blood pressure \>160 millimeters of mercury (mmHg) or diastolic blood pressure \>100 mmHg.
4. Myocardial infarction within 6 months.
5. New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
6. Uncontrolled angina pectoris within 6 months.
7. Cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
8. Diagnosed or suspected long QT syndrome or known family history of long QT syndrome.
9. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
10. Bradycardia of \<50 beats per minute (bpm) unless the participant has a pacemaker.
11. History of second- or third-degree heart block. Participants with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
12. Coronary/peripheral artery bypass graft within 6 months.
13. Complete left bundle branch block.
7. Has history of other active malignancy within 3 years prior to randomization, except the following:
1. Adequately resected nonmelanoma skin cancer.
2. Adequately treated intraepithelial carcinoma of the cervix.
3. Any other curatively treated in situ disease.
4. Prostate carcinoma with a prostate-specific antigen value \<0.2 nanograms per milliliter (ng/mL).
8. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) Grade ≤1 or baseline.
9. Any known contraindication to treatment, including hypersensitivity to either the drug substances or inactive ingredients in the drug products.
Note: Other protocol specified inclusion/exclusion criteria may apply.
A Study to Assess Adverse Events, Change in Disease Activity and Optimal Dose of Intravenous (IV) Telisotuzumab Adizutecan With IV Pembrolizumab for First-Line Treatment of Adult Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Telisotuzumab adizutecan, a c-Met-targeted antibody-drug conjugate with a topoisomerase-inhibitor payload, is studied in combination with pembrolizumab versus standard chemotherapy plus pembrolizumab as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma with c-Met expression.
NCT07744126 · Phase 2 · AbbVie
Recruiting sites: California, Georgia
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma that is considered incurable by local therapies.
* Eastern cooperative oncology group (ECOG) performance status must be \<= 1.
* Must have c-Met protein expression by central c-Met immunohistochemistry (IHC) staining at any intensity in \>= 25% tumor cells.
* Must have measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
* Must have had no prior systemic therapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Exclusion Criteria:
* Have history of interstitial lung disease or pneumonitis that required treatment with systemic steroids, or any evidence of active interstitial lung disease or pneumonitis on screening chest computed tomography (CT) scan.
* Have any major, life-threatening conditions.
* Life expectancy should be at least 3 months.
NeoAdjuvant, Spare-Adjuvant (NASA) in Stage IIIB-IV (M1a) Melanoma
This phase 2 trial randomizes patients with resectable stage IIIB-M1a cutaneous or unknown-primary melanoma to neoadjuvant PD-1-based therapy—either pembrolizumab alone or ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1)—without planned adjuvant therapy after lymphadenectomy.
NCT07740941 · Phase 2 · UNC Lineberger Comprehensive Cancer Center
Recruiting sites: North Carolina
Read full eligibility criteria
Inclusion Criteria:
* Written informed consent will be obtained to participate in the study, and HIPAA authorization for the release of personal health information.
* Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee, including randomization.
* Age ≥ 18 years at the time of consent.
* ECOG Performance Status of 0-2.
* Histological confirmation of cutaneous melanoma or melanoma of unknown primary.
* AJCC stage IIIB/IVa resectable disease that is measurable by iRECIST criteria.
* Adequate hematologic, renal, hepatic, and heart function
Exclusion Criteria:
* Prior treatment with PD-1 Programmed cell death Protein 1 (PD-1) and Cytotoxic T-lymphocyte Antigen 4 (CTLA-4).
* Has an active autoimmune disease that requires systemic treatment with the use of disease-modifying agents or immunosuppressive drugs. For corticosteroids, up to 10 mg of prednisone daily, or an equivalent dose, is permitted. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Any condition, including laboratory abnormalities, that, in the opinion of the investigator, places the subject at unacceptable risk if he/she were to participate in the study. This includes, but is not limited to, serious medical conditions or psychiatric illnesses that are likely to interfere with participation in this clinical study.
Phase 3 Study of Cadonilimab Combined With Chemotherapy vs Chemotherapy in Combination With or Without Nivolumab for the 1L Treatment of Participants With HER2-negative, Previously Untreated, Unresectable or Metastatic Gastric/GEJ Adenocarcinoma
Cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, is combined with CAPOX chemotherapy and compared against chemotherapy with or without nivolumab as first-line treatment for HER2-negative, unresectable or metastatic gastric/GEJ adenocarcinoma.
NCT07700979 · Phase 3 · Akeso
Recruiting sites: Arizona, California, Colorado, Connecticut, Massachusetts, Michigan, New York, Oregon, Tennessee, Texas, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
1. Able to provide written informed consent and can understand and comply with the requirements of the study.
2. Histopathologically-confirmed diagnosis of locally advanced unresectable or metastatic G/GEJ adenocarcinoma.
3. No prior systemic therapy for locally advanced unresectable or metastatic G/GEJ adenocarcinoma. NOTE: For participants who have received prior neoadjuvant/adjuvant therapy for curative intent, the time between disease progression and last treatment should be at least 6 months.
4. ECOG PS of 0 or 1 within 3 days prior to randomization.
5. Age ≥ 18 years at the time of voluntarily signing informed consent.
6. Evaluable PD-L1 expression results.
7. Participants must have at least one measurable lesion per RECIST v1.1 as assessed by investigator assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
8. Adequate organ function as indicated by the following laboratory values. Specimens must be collected within 7 days prior to the first dose of study treatment.
9. Life expectancy ≥3 months.
10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during treatment, and for at least 150 days after the last dose of cadonilimab/nivolumab, 270 days after the last dose of oxaliplatin, and 180 days after the last dose of capecitabine.
11. Non-sterile males must agree to use effective contraception during treatment and for at least 120 days following the last dose of cadonilimab/nivolumab/capecitabine and 180 days after the last dose of oxaliplatin.
Exclusion Criteria:
1. Histopathologically confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma.
2. Known HER2 positive. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH).
3. Participants with active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
4. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time/month).
5. Clinically significant bleeding symptoms within 28 days before the first dose or a definite tendency to bleed.
6. Have a history of ≥ Grade 2 gastrointestinal perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization.
7. Participants who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
Torvutatug Samrotecan Plus Bevacizumab as First-line Maintenance in Homologous Recombination Deficiency (HRD) Negative Advanced Epithelial Ovarian Cancer
Torvutatug samrotecan, a folate receptor alpha-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor payload, is being studied in combination with bevacizumab versus bevacizumab alone as first-line maintenance therapy in HRD-negative advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
NCT07851025 · Phase 3 · AstraZeneca
Recruiting sites: Florida, Maryland, Montana, Ohio
Read full eligibility criteria
Key Inclusion Criteria:
* Participants with newly diagnosed FIGO Stage III/IV, histologically confirmed epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma
* Provision of an archival FFPE tumour sample
* Participants who have completed at least 6 cycles and a maximum of 8 cycles of first-line Platinum-based chemotherapy (PBC) prior to randomisation
* Participants must have received a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of PBC, prior to randomisation
* Participants who have completed cytoreductive surgery or have inoperable disease
* Participants with non-progressive disease upon completion of front-line induction therapy
* HRD negative tumour
Key Exclusion Criteria:
* Participants with tumours of non-epithelial origin, borderline tumours, or low-grade epithelial tumours.
* Participants with history of (non-infectious) ILD/pneumonitis that required steroids or supplemental oxygen, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
* Participants with non-healing wound, active ulcer, or bone fracture
* Participants with evidence of active or ongoing bowel obstruction
* Prior exposure to any FRα-targeted therapy, including MIRV, or any TOP1i Antibody-drug Conjugate (ADC)
Upfront Chemotherapy With Radiation Therapy (CRT) Followed by Chemotherapy in Localized Esophageal Adenocarcinoma
This phase 2 trial adds consolidative chemotherapy (modified FOLFOX-6 or FLOT) after standard chemoradiation (carboplatin/paclitaxel) for newly diagnosed, localized (stage II-IVA) esophageal or gastroesophageal junction adenocarcinoma.
NCT07603375 · Phase 2 · Duke University
Recruiting sites: North Carolina
Read full eligibility criteria
Inclusion Criteria:
* Subject must be able to provide study specific informed consent prior to study entry
* Must be newly diagnosed, histologically proven diagnosis of adenocarcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II);
* Stage II-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition;
* Complete history and physical examination within 21 days of signing consent;
* Staging whole-body FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) scan with or without contrast (preferred) or chest/abdominal (CT with contrast) confirming there is no evidence of metastatic disease must be obtained within 45 days of study enrollment
* ECOG (Eastern Cooperative Oncology Group) performance status of 0-2
* Subjects must be appropriate candidates for planned chemoradiation (concurrent carboplatin/paclitaxel) and chemotherapy (FLOT, m-FOLFOX-6) as determined by the treating radiation oncologist, medical oncologist, and surgical oncologist.
* Adequate hematologic, renal, and hepatic function within 14 days of initiation of therapy
Exclusion Criteria:
* Cervical esophageal cancers arising 15-18 cm from the incisors.
* Esophageal squamous cell carcinoma.
* Patients with T4b disease according to the AJCC 8th Edition.
* Definitive clinical or radiologic evidence of metastatic disease.
* Has had prior systemic therapy or radiation therapy for the current diagnosis.
* Prior thoracic radiotherapy for any reason that would result in overlap of radiation therapy fields; all patients with prior radiotherapy must be reviewed by the PI to determine if patient is eligible.
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
* Severe, active co-morbidity defined as follows:
* Active uncontrolled infection requiring IV antibiotics;
* Pregnant and/or nursing subjects;
* HIV positive with CD4 count \< 200 cells/microliter. Note that subjects who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Has a history or current evidence of physical or physiological contraindication to participation in this study, at the discretion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
A Study of JNJ-101556143 in Participants With Metastatic Prostate Cancer
JNJ-101556143, an orally administered AR-BRD4 targeting bifunctional small molecule (RIPTAC), is being studied in metastatic androgen pathway modulation-resistant prostate cancer.
NCT07832292 · Phase 2 · Janssen Research & Development, LLC
Recruiting sites: Louisiana, Massachusetts, New York, Tennessee
Read full eligibility criteria
Inclusion Criteria:
* Have histologically confirmed adenocarcinoma of the prostate. Primary (or pathologic evidence of conversion to) small cell carcinoma, carcinoid tumor, mixed neuroendocrine carcinoma, large cell neuroendocrine carcinoma, or sarcoma of the prostate is disallowed
* Progressive metastatic androgen pathway modulation-resistant prostate cancer (mAPMR) defined as having a Prostate-Specific Antigen (PSA) level greater than or equal (\>=) 10 nanograms per milliliter (ng/mL) and at least one of the following: (a) PSA progression defined as at least 2 consecutive increases in PSA value over a previous reference value measured at least 1 week apart. (b) Progressive disease or new lesion(s) in the lymph nodes, bones, or viscera on conventional imaging (computed tomography \[CT\]/magnetic resonance imaging \[MRI\]) as defined by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) and/or on bone scan per Prostate Cancer Working Group 4 (PCWG4) while on Androgen Deprivation Therapy (ADT) (either surgically \[bilateral orchiectomy\] or with medication). Local-regional disease including invasive disease of rectum, bladder, pelvis is allowed as long as participant has a current or past history of distant metastasis (M1 disease). Participants in Part 1 must have measurable disease per RECIST v1.1 by conventional imaging with CT or MRI (chest, abdomen, and pelvis) and/or Technetium-99\^m (99\^mTc) bone scan confirmed by Blinded Independent Central Review (BICR) at the time of screening
* Prior bilateral orchiectomy or medical castration (receiving ongoing ADT with a Gonadotropin-Releasing Hormone (GnRH) analog \[agonist or antagonist\]) with castrate level of serum testosterone (less than \[\<\] 50 nanograms per deciliter \[ng/dL\] or 1.7 nanomoles per liter \[nmol/L\]) prior to the first dose of trial intervention and must continue this therapy throughout the treatment phase
* Have discontinued concurrent use of any non-investigational systemic anticancer therapy (that is, cytotoxic chemotherapy, Androgen Receptor Pathway Inhibitor (ARPI), radiation therapy) within 2 weeks or Lutetium-177 Prostate-Specific Membrane Antigen-617 (177\^Lu PSMA-617) within 6 weeks prior to first dose of trial intervention, or any investigational drugs within 3 months of first dose of trial intervention
* Toxicity related to prior anticancer treatment that is deemed clinically relevant must have resolved to common terminology criteria for adverse events (CTCAE) Version 6.0 Grade 1 or better
Exclusion Criteria:
* Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
* Suspected or known allergies, hypersensitivity, or intolerance to JNJ-101556143 or its excipients
* Had major surgery or had significant traumatic injury less than or equal to 28 days of the first dose of trial intervention. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate
* Spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
* Solid organ or bone marrow transplantation
Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma
Casdatifan, an oral allosteric HIF-2α inhibitor, is being studied as a phase I treatment in patients with refractory metastatic clear cell renal cell carcinoma who progressed on prior IO- and VEGF-based therapies.
NCT07748988 · Phase 1 · Vanderbilt-Ingram Cancer Center
Recruiting sites: Tennessee
Read full eligibility criteria
Inclusion Criteria:
1. Signed and dated written informed consent.
2. Male or female ≥ 18 years of age on the day of signing informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
4. Histologically confirmed metastatic clear cell renal cell carcinoma (ccRCC)
5. Patients must have received at least one immune oncology (IO) agent and at least one VEGF-targeted therapy (alone or in combination)
6. Measurable tumor burden which can be followed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST 1.1 as assessed by the local site investigator
7. At least one metastatic lesion that is amenable to percutaneous biopsy
8. Adequate organ and bone marrow function resulted ≤ 28 days prior to first dose of protocol-indicated treatment:
* Absolute neutrophil count (ANC) ≥ 1500/µL.
* Platelets ≥ 100,000/µL.
* Hemoglobin ≥ 10.0 g/dL or ≥ 6.2 mmol/L.
* Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants).
* Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), or direct bilirubin ≤ ULN for participants with total bilirubin \> 1.5 xULN.
* AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional upper limit of normal (ULN)
9. Women must not be breastfeeding and further agree to not breastfeed during study treatment; and for at least 7 days after patient's final dose of casdatifan.
10. A woman of childbearing potential (WOCBP) - see Appendix 3 for definition of WOCBP - must have a negative serum or urine pregnancy test during screening within 28 days prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception (Appendix 3) from the time of signing consent, and until at least 7 days after her final dose of casdatifan.
11. Men must refrain from donating sperm for at least 7 days after patient's final dose of casdatifan.
12. A man able to father children (see Appendix 3 for definition) who is sexually active with a WOCBP must agree to follow instructions for using acceptable contraception (Appendix 3), from the time of signing consent, and until at least 7 days after his final dose of casdatifan.
13. No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry ≤ 88%.
14. No active pneumonitis at screening as assessed by CT scan.
15. No medical history of severe chronic obstructive pulmonary disease (COPD).
16. If a participant has CNS metastases the participant must meet the following criteria:
* Participants with previously treated brain metastases may participate provided they are clinically stable and without steroid treatment for at least 14 days prior to the first dose of study treatment. Participants with carcinomatous meningitis are excluded.
Exclusion Criteria:
1. Prior treatment with HIF 2α inhibitors (e.g. belzutifan or related agents)
2. Is currently participating in or within 2 weeks prior to receiving first dose of study treatment in a study of an investigational agent or investigational device.
• Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks after the last dose or last exposure to the previous investigational agent or investigational device.
3. Known severe hypersensitivity (≥ Grade 3) to any of the excipients of casdatifan.
4. History of myocarditis or pericarditis or other known underlying heart disease that is clinically significant by investigator judgment (for example, cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III or IV, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction). History of cerebrovascular accident (including TIA) within the past 6 months (24 weeks) prior to starting study treatment.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection/sepsis, interstitial lung disease, recent hospitalizations with unresolved symptoms, poorly controlled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Inability to swallow study treatment.
7. Contraindications to biopsy (e.g. bleeding diathesis, uncorrectable coagulopathy)
IL-15 Superagonist With or Without Vaccine in Biochemically Recurrent Prostate Cancer After Previous Stereotactic Body Radiation Therapy
N-803, an IL-15 superagonist fusion protein, is given alone or combined with the ETBX-71 vaccine to treat biochemically recurrent prostate cancer following prior stereotactic body radiation therapy.
NCT07686380 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: Maryland
Read full eligibility criteria
* INCLUSION CRITERIA:
* Histopathological confirmation of prostate adenocarcinoma by the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center prior to the study treatment initiation. If no pathologic specimen is available, participants may enroll with a pathologist s report showing a histologic diagnosis of prostate adenocarcinoma and a clinical course consistent with the disease from any outside site.
* Biochemically recurrent prostate cancer, defined as PSA over 0.8 ng/ml following radical prostatectomy or \>= 2 ng/ml above the nadir following definitive radiotherapy or definitive radiotherapy (including brachytherapy) for localized prostate cancer.
* Participants must be at least 1 year removed from definitive local therapy before the study treatment initiation.
* Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation.
* Hepatic function eligibility parameters: Bilirubin (total and direct) \<= upper limit of normal (ULN) (OR in participants with Gilbert s syndrome, a total bilirubin \<= 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) \<= 1.5 times upper limit of normal.
* Adequate renal function defined by a calculated creatinine clearance \> 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
* ECOG performance score 0-1.
* No other active malignancies within the 36 months prior to the study treatment initiation (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder).
* 18 years of age or older.
* Individuals must agree to use effective contraception (barrier, vasectomy and/or abstinence) for the duration of study therapy and for four months after the last treatment administration. Individuals with partners with birthing potential will be recommended that their partner use a highly effective contraception (includes use of oral, injected or implanted hormonal methods of contraception, placement of certain intrauterine devices (IUD) or intrauterine systems (IUS), hysterectomy, oophorectomy, salpingectomy.
* Individuals must agree to not donate sperm during the restricted period (for the duration of study therapy and for four months after the last dose of study treatment).
* Negative CT scan/ Magnetic resonance imaging (MRI) for evidence of soft tissue metastasis (visceral or lymph node).
* Negative Tc99 for evidence of bone disease.
* Participants must have had prior SBRT to PSMA+ findings beyond the prostate and have had a documented 25% or more PSA rise from post-SBRT nadir
* Baseline testosterone \>= 100 ng/dl.
* Hematological parameters:
* Granulocyte count \>= 1000/mm\^3
* Platelet count \>= 100000/mm\^3
* Hemoglobin (Hgb) \>= 10 g/dL
* Participants must be able to understand and willing to sign a written informed consent document.
EXCLUSION CRITERIA:
* Immunocompromised status due to:
* Human immunodeficiency virus (HIV) seropositivity
* HBV or HCV seropositivity
* Other immunodeficiency diseases
* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed. Participants with diabetes type I, vitiligo, or alopecia are allowed.
* Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
* Chronic administration (defined as daily or every other day for continued use \> 14 days) of systemic corticosteroids within 28 days before the study treatment initiation. Note: Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
* Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 28 days prior to the study treatment initiation.
* Major surgery within 28 days prior to study treatment initiation.
* Systemic therapy, including any investigational therapy within 28 days prior to the study treatment initiation.
* Radiation therapy within 14 days prior to the study treatment initiation.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.
* Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to the first planned dose of study drugs), myocardial infarction (\< 6 months prior to the first planned dose of study drugs), or any of the following at time of enrollment: unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II), serious cardiac arrhythmia, or uncontrolled hypertension (SBP\>170/ DBP\>105).
* Serious intercurrent medical illness evaluated by medical history and physical exam that would interfere with participant's ability to carry out the treatment program.
Ph1/2 Trial Of Navlimetostat With Pumitamig In MTAP-Deficient Advanced Non-Small Cell Lung Cancer
This phase 1/2 trial tests navlimetostat, an oral MTA-cooperative PRMT5 inhibitor, combined with pumitamig, a bispecific anti-PD-L1/VEGF-A antibody, in patients with MTAP-deficient advanced non-small cell lung cancer who have progressed on prior systemic therapy.
NCT07579221 · Phase 1/2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
General inclusion criteria
* Age ≥18 years. Because no dosing or adverse event data are currently available on the use of navlimetostat in combination with pumitamig in patients \<18 years of age, children are excluded from this study.
* Have at least one measurable lesion as the target lesion based on RECIST v1.1. Lesions treated with prior local treatment (radiation, ablation, etc) are generally not considered target lesions. If the lesion with prior local treatment is the only target lesion, evidence must be provided to demonstrate disease progression.
* MTAP loss as defined by homozygous deletion on NGS and/or by absent MTAP protein expression by IHC. Test can be performed on an archival tissue. External testing by a commercial vendor (e.g. Foundation Medicine, Caris, BostonGene, Tempus) or internal assay (e.g. UT MD Anderson MAPP or IHC) is accepted.
* ECOG performance status 0-1.
* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
* Patients must have previously received at least one course of systemic therapy for advanced or metastatic disease. Perioperative treatment is accepted if patient progresses within 6 months.
* Patients must have received at least one prior line of standard therapy. Prior exposure to anti-PD-1 or anti-PD-L1 therapies or other checkpoint inhibitors is permitted.
* Patients with actionable genomic alterations for which targeted therapy is considered standard front-line must have received appropriate targeted therapy EGFR, ALK, RET, NTRK, MET or ROS1). Patients may also have been treated with one or more lines of chemotherapy.
* Adequate organ and marrow function as defined below
* Hemoglobin ≥9.0 g/dL with no packed red blood cell transfusions in the past 7 days.
* Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L.
* Platelet count ≥100,000 with no platelet transfusions in the past 7 days.
* Total bilirubin ≤1.5 x institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤3 × ULN.
* AST (SGOT)/ALT (SGPT) \<3 x institutional ULN value unless liver metastases are present, in which case \<5 x ULN.
* Calculated creatinine clearance ≥45 mL/min (using Cockroft-Gault formula or 24-hour urine collection).
* Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g
* Coagulation function: international normalized ratio (INR) or prothrombin time and activated partial thromboplastin time ≤ 1.5 x ULN unless the participant is receiving anticoagulation therapy as long as the prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
* Agree to follow the study protocol, including treatment, scheduled visits, and examinations, for the duration of the study.
Reproductive status
Note: The investigator or designee shall counsel individual of childbearing potential (IOCBP) participants (as defined in Appendix 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • Female (as assigned at birth) participants Note: Individuals who are not of childbearing potential are exempt from contraceptive requirements.
o IOCBP must have a negative highly sensitive urine or serum (as required by local regulation) pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
Note: If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Note: The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of an individual with an undetected pregnancy.
* IOCBP participants must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
* IOCBP are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional nonhormonal highly effective method of contraception (as described in Appendix 3).
o A female (as assigned at birth) is eligible to participate if they are not pregnant or breastfeeding and at least 1 of the following conditions applies:
* Is not an IOCBP OR
* Is an IOCBP using a combination of a hormonal and a non-hormonal contraceptive method or a non-hormonal method alone that is highly effective (with a failure rate of \< 1% per year), as described in Appendix 3, during the intervention period and for at least 6 months after the last dose of study intervention. IOCBP participants must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period. If needed, IOCBP participants should be advised to seek advice about egg donation and cryopreservation of germ cells before treatment.
* Male (as assigned at birth) participants:
Note: Azoospermic males are not exempt from contraceptive requirements and will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with IOCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
* Male (as assigned at birth) participants will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with IOCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male (as assigned at birth) participants should continue to use a condom during the intervention period and for at least 6 months after the last dose of study intervention.
* IOCBP partners of male (as assigned at birth) participants should be advised to use a highly effective method of contraception during the intervention period and for at least 6 months after the last dose of study intervention for the male participant. IOCBP partners are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional non-hormonal highly effective method of contraception (as described in Appendix 3).
* Male (as assigned at birth) participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 6 months after the last dose of study intervention.
* Male (as assigned at birth) participants must refrain from donating sperm during the intervention period and for at least 6 months after the last dose of study intervention. If needed, male (as assigned at birth) participants should be advised to seek advice about sperm donation and cryopreservation of germ cells before treatment.
* Breastfeeding partners of male (as assigned at birth) participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms. • Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
* Prior treatment with PRMT5 and/or MAT2A inhibitors.
* Prior treatment with anti-PD-1/VEGF or anti-PD-L1/VEGF bispecific antibodies
* Exposure to systemic anticancer therapy within 21 days or 5 half-lives (whichever is longer) prior to trial enrollment is not permitted.
* Significant risk of pulmonary hemorrhage (per investigators clinical judgement) indicated by the following criteria:
* Tumors with clear radiographic evidence of major blood vessel invasion, as demonstrated by any of the following radiological features: luminal irregularity, discontinuity, distortion or truncation, intraluminal mass formation or any other abnormal imaging funding assessed by the investigator to indicate risk of bleeding.
* Tumor lesions with clear invasion of major airways (such as tracheal invasion) or vital organs (such as the heart, pericardium, and esophagus)
* At least one major cavitation posing hemorrhage risk
* Clinically significant hemoptysis defined as coughing up or expelling ≥ 1 teaspoon (5 mL) of blood or small blood clots within 4 weeks prior to study treatment initiation. Note: participants with blood in the sputum are allowed to be enrolled.
* Recent (within 3 months) history of intracranial/spinal or GI bleed, vascular disease with a risk of rupture, or therapeutic anticoagulation/antiplatelet treatment within 10 days before initiation of treatment. Participants receiving anticoagulation at a stable dose may be eligible if their PT and aPTT values are stable and within the intended therapeutic range, and if hemorrhagic risk is assessed as low per investigator's clinical judgement.
* Have any of the following hypertension or diabetic conditions prior to trial treatment:
* Uncontrolled hypertension (systolic BP ≥ 160mmHg and/or diastolic BP
≥ 100mmHg) while on antihypertensive medication
* Those with a history of hypertensive crisis or hypertensive encephalopathy
* Poorly controlled diabetes (fasting blood glucose ≥ 13.3mmol/L / 240 mg/dL or HgA1c ≥ 8.5%)
* Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, ductal carcinoma in situ, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Major surgery within 21 days of starting treatment is not permitted. Patients must have recovered from the effects of any major surgery.
* Patients with an average QTc (using Fridericia correction) \>470 msec are excluded.
* Patients with clinically significant uncontrolled medical conditions are excluded, including: active infection requiring IV antibiotics; significant cardiovascular disease (including uncontrolled hypertension or heart failure, ventricular arrythmia, unstable angina or MI within 6 mo prior to study treatment initiation); extensive bilateral interstitial lung disease; psychiatric illness that limits compliance; history GI/non-GI fistula, GI perforation, or intraabdominal abscess within 6 mo prior to initiation on study; evidence or history of bleeding diathesis or coagulopathy considered a safety risk as per investigatory clinical judgement including history of thromboembolic or major hemorrhagic events within 6 months of initiation on study; or any other condition deemed high risk by the Investigator.
* Known central nervous system (CNS) metastases or leptomeningeal disease is exclusionary unless adequately treated and the patient is no longer on steroids or anticonvulsants. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
* Patients unable to swallow oral medication or with gastrointestinal disorders likely to interfere with drug absorption are excluded.
* Pregnant or breastfeeding women are excluded.
* Ongoing need for a medication with a known risk of Torsade's de Pointes or known as a strong inhibitor or strong inducer of CYP3A4 and/or P-glycoprotein or a proton-pump inhibitor that cannot be switched to alternative treatment prior to study entry. The following drug interaction databases and other literature can be utilized to determine the CYP3A4/Pgp inhibitors and inducers:
o https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-anddruginteractions-table-substrates-inhibitors-and-inducers https://druginteractions.medicine.iu.edu/MainTable.aspx
* Active viral hepatitis, including the following:
* Any positive test result for hepatitis B virus (HBV) indicating presence of virus, e.g., HBV DNA positive would be excluded. Participants with negative HBV viral load are eligible to enroll, as are participants with anti-HBs positive in line with prior vaccination or resolved infection.
* Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV RNA).
* Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll.
* Known human immunodeficiency virus (HIV) positive with an AIDS-defining opportunistic infection within the last year, or a current CD4 count \< 350 cells/μL. Participants with HIV are eligible if they have received established antiretroviral therapy (ART) for at least 4 weeks prior to study treatment initiation and continue on ART as clinically indicated while enrolled on study. Viral serology only to be conducted if locally mandated and, if done, must be performed within 28 days of study treatment initiation.
* Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to the first dose of study intervention.
* Live/attenuated vaccine received within 30 days of first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.
* Any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 2 weeks prior to treatment. The concurrent use of any botanical preparation is not permitted while on study.
* Prior organ allograft.
* History of allergy to study intervention or any of its components.
* History of severe (Grade ≥3) irAEs observed with previous PD-1/PD-L1 checkpoint inhibitors that led to treatment discontinuation and rechallenge with ICI was not possible.
* Active, known autoimmune disease. Note: participants with endocrine disorders treated with hormone replacement (e.g. Type I DM, hypothyroidism only requiring hormone replacement), skin disorders not requiring systemic therapy or conditions not expected to recur are allowed.
* Advanced/clinically significant lung disease (e.g. pneumonitis requiring systemic steroids, uncontrolled COPD or asthma, restrictive lung disease or pulmonary hypertension) within 6 mo prior to study treatment initation, or any history of ILD or pneumonitis requiring treatment with systemic steroids (\>/= G2), or who have current or suspected ILD or pneumonitis.
* History of peripheral artery disease (e.g., claudication, Leo Beuerger's Disease).
* Any condition for which, in the investigator's opinion, participation would not be in the patient's best interest (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
* Participation in another interventional clinical tria
Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial
This phase III trial compares pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin, a DNA-alkylating antibiotic delivered directly into the peritoneal cavity, against standard IV FOLFIRI plus bevacizumab in patients with unresectable appendix or colorectal cancer with peritoneal metastases who are not candidates for cytoreductive surgery.
NCT07271355 · Phase 3 · City of Hope Medical Center
Recruiting sites: Arizona, California, Georgia, Illinois
Read full eligibility criteria
Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies
* If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed appendiceal or colorectal cancer peritoneal metastases
* No extraperitoneal metastases except lung ≤ 5 lesions with largest ≤ 1cm as identified on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
* Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by RECIST (v1.1)
* Completed at least 4 months (8 cycles) of first-line standard-of-care oxaliplatin-based systemic therapy without progression of disease. Or completed less than 4 months of oxaliplatin based therapy due to intolerance and without progressive disease. Or progressed on first-line standard-of-care oxaliplatin-based systemic therapy. Permissible first-line systemic therapies include leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) or fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI). Receipt of anti-EGFR, anti-VEGF, or anti-BRAF therapy in the first-line is acceptable. Mismatch repair-deficient patients are permissible if they have progressed on first-line immunotherapy
* Not a candidate for cytoreductive surgery as determined by site investigator
* Fully recovered from the acute toxic effects of prior anti-cancer therapy to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or lower except alopecia, hearing loss, neuropathy, or non-clinically significant laboratory abnormalities
* Complete medical history and physical exam (To be performed within 28 days prior to Day 1 of protocol therapy)
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
* Platelets ≥ 100,000/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
* Hemoglobin ≥ 8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
* Serum albumin ≥ 2.8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
* Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, then direct bilirubin \< 1.5 mg/dL) (To be performed within 28 days prior to Day 1 of protocol therapy)
* Aspartate aminotransferase (AST) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
* Alanine aminotransferase (ALT) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
* Calculated creatinine clearance of ≥ 45 mL/min per 24-hour urine test or the Cockcroft-Gault formula (To be performed within 28 days prior to Day 1 of protocol therapy)
* Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (To be performed within 28 days prior to Day 1 of protocol therapy)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
* CROSS-OVER ARM INCLUSION: Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* CROSS-OVER ARM INCLUSION: Agreement to allow the use of archival tissue from diagnostic tumor biopsies
* If unavailable, exceptions may be granted with Study PI approval
* CROSS-OVER ARM INCLUSION: Age: ≥ 18 years
* CROSS-OVER ARM INCLUSION: ECOG performance status of 0 or 1
* CROSS-OVER ARM INCLUSION: No extraperitoneal metastases except lung ≤ 5 lesions with largest ≤ 1cm as identified on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
* CROSS-OVER ARM INCLUSION: Progression on Control Arm of the Study as determined by RECIST v1.1. Non-radiographic progression will need to be assessed on a case-by-case basis by central review
* CROSS-OVER ARM INCLUSION: Fully recovered from the acute toxic effects of prior anti-cancer therapy to CTCAE grade 1 or lower except alopecia, hearing loss, neuropathy, or non-clinically significant laboratory abnormalities
* CROSS-OVER ARM INCLUSION: Complete medical history and physical exam (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: ANC ≥ 1,500/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Platelets ≥ 100,000/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Hemoglobin ≥ 8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Serum albumin ≥ 2.8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Total bilirubin ≤ 1.5 X ULN (unless has Gilbert's disease, then direct bilirubin \<1.5 mg/dL) (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: AST ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: ALT ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Calculated creatinine clearance of ≥ 45 mL/min per 24-hour urine test or the Cockcroft-Gault formula (To be performed within 28 days prior to Day 1 of protocol therapy)
* CROSS-OVER ARM INCLUSION: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (To be performed within 28 days prior to Day 1 of protocol therapy)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* CROSS-OVER ARM INCLUSION: Agreement by females and males of childbearing potential to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion Criteria:
* More than 8 cycles of first line irinotecan therapy
* Progression on irinotecan
* Receipt of any second-line systemic chemotherapy (Note: Sequential administration of FOLFOX followed by FOLFIRI is considered second line therapy. However, FOLFOXIRI followed by FOLFIRI is considered first line as long as no more than 8 cycles of irinotecan are given)
* Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
* Strong CYP3A4 inducers/inhibitors within 14 days prior to Day 1 of protocol therapy
* Prior peritoneal-directed chemotherapy (Prior cytoreductive surgery is permitted)
* Participation in another clinical study with an investigational product administered in the last 2 months
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
* Low-grade appendiceal mucinous neoplasm or low-grade appendiceal mucinous adenocarcinoma
* Extraperitoneal metastases (except lung ≤ 5 lesions with largest being ≤ 1cm)
* Any history of bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy, or need for total parenteral nutrition. Even if the bowel obstruction resolved with conservative measures, the patient would be excluded. The exception is if the bowel obstruction was surgically addressed with ostomy, resection or bypass. This exception should be documented
* Fused mesenteric disease-causing mesenteric shortening and bowel sequestration ("cauliflowering")
* Bulky mesenteric disease where chemotherapy is unlikely to penetrate the tumor
* Contraindication to laparoscopy
* Rapid weight loss (\> 10% in \< 3 months)
* Ascites (\> 2L drained per month)
* Adhesions involving \> 50% of abdominal cavity on diagnostic laparoscopy
* Life expectancy \< 6 months
* Treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 Cycle 1 of treatment
* Patients receiving prophylactic antibiotics are eligible, provided the signs of active infection have resolved
* Any prior malignancy except adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years
* History of allergic or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to study agents (platinum-based compounds, etc.)
* History of allogeneic organ transplantation or other active primary immunodeficiency
* Active and uncontrolled infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies)
* Clinically significant uncontrolled illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
* CROSS-OVER ARM EXCLUSION: Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
* CROSS-OVER ARM EXCLUSION: Strong CYP3A4 inducers/inhibitors within 14 days prior to Day 1 of protocol therapy
* CROSS-OVER ARM EXCLUSION: Participation in another clinical study with an investigational product administered in the last 2 months other than the current study
* CROSS-OVER ARM EXCLUSION: Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
* CROSS-OVER ARM EXCLUSION: Extraperitoneal metastases (except lung ≤ 5 lesions with largest being ≤ 1cm)
* CROSS-OVER ARM EXCLUSION: Any history of bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy, or need for total parenteral nutrition. Even if the bowel obstruction resolved with conservative measures, the patient would be excluded. The exception is if the bowel obstruction was surgically addressed with ostomy, resection or bypass. This exception should be documented
* CROSS-OVER ARM EXCLUSION: Fused or bulky mesenteric disease-causing mesenteric shortening and bowel sequestration
* CROSS-OVER ARM EXCLUSION: Contraindication to laparoscopy
* CROSS-OVER ARM EXCLUSION: Rapid weight loss (\> 10% in \< 3 months)
* CROSS-OVER ARM EXCLUSION: Ascites (\> 2L drained per month)
* CROSS-OVER ARM EXCLUSION: Adhesions involving \> 50% of abdominal cavity on diagnostic laparoscopy
* CROSS-OVER ARM EXCLUSION: Life expectancy \< 6 months
* CROSS-OVER ARM EXCLUSION: Treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 Cycle 1 of treatment
* Patients receiving prophylactic antibiotics are eligible, provided the signs of active infection have resolved
A Study of Raludotatug Deruxtecan With or Without Bevacizumab as First-Line Maintenance Treatment in Non-HRD-Positive Advanced Ovarian Cancer (MK-5909-006, (ENGOT-ov102/GOG-3141/ REJOICE-Ovarian 04)
Raludotatug deruxtecan (R-DXd), a CDH6-targeted antibody-drug conjugate carrying a topoisomerase I inhibitor payload, is being studied with or without bevacizumab as first-line maintenance therapy in non-HRD-positive advanced (FIGO III/IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer after response to first-line platinum-based chemotherapy.
NCT07776691 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: District of Columbia, Texas
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a new, histologically confirmed diagnosis of International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV epithelial ovarian cancer (EOC) (high grade serous or high grade endometrioid), fallopian tube cancer, or primary peritoneal cancer
* Has undergone primary debulking surgery (PDS) or interval debulking surgery (IDS)
* Has completed first-line (1L) platinum-based chemotherapy, with a response of stable disease, partial response, complete response or no evidence of disease per protocol
* Has provided tumor tissue that is not previously irradiated
* Who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except alopecia or vitiligo), as assessed by the physician investigator
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has non-serous or non-endometrioid high-grade epithelial histology, nonepithelial ovarian cancers, borderline tumors, mucinous tumor, seromucinous tumor that is predominately mucinous, malignant Brenner's tumor, and undifferentiated carcinoma
* Has received 1L platinum-based chemotherapy without bevacizumab and have a response of SD or PR at the time of screening
* Has received prior systemic anticancer therapy, with the exception of the first-line platinum-based chemotherapy required by the inclusion criteria
* Has not recovered from major surgery or has ongoing surgical complications
* Has a homologous recombination deficiency (HRD)-positive, unknown, or inconclusive tumor status as determined by the central laboratory
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder or prior pneumonectomy
* Has current, clinically relevant bowel obstruction including obstruction related to underlying EOC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam
* HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman disease
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active infection requiring systemic therapy
A Study of Risvutatug Rezetecan in Combination With Ivonescimab in Participants With Advanced Solid Tumors (EMBOLD PanTumour-103)
Risvutatug rezetecan, an anti-B7-H3 antibody-drug conjugate bearing a topoisomerase inhibitor payload, is combined with ivonescimab, a PD-1/VEGF bispecific antibody, in a phase 1/2 study of advanced/metastatic solid tumors including NSCLC and extensive-stage small cell lung cancer.
NCT07602855 · Phase 1/2 · GlaxoSmithKline
Recruiting sites: California, North Carolina, Ohio
Read full eligibility criteria
Inclusion Criteria:
Participants are eligible to be included in the study only if all the following criteria apply:
* Male or female participants at least 18 years of age (≥18 years) at the time of signing the informed consent form (ICF).
* Participants with histologically confirmed advanced/metastatic solid tumors, irrespective of mutational status, as defined per cohort, as follows:
ES-SCLC
* Histologically or cytologically confirmed SCLC (prior pathological diagnosis of complex SCLC \[such as mixed SCLC and NSCLC\] or transformed SCLC \[NSCLC to SCLC\] is not allowed)
* ES-SCLC \[per Veterans Administration Lung Study Group (VALG) criteria\] at study entry Squamous NSCLC or non-squamous NSCLC
* Histologically or cytologically confirmed Squamous or Non-squamous NSCLC.
* Metastatic NSCLC (Stage IV), according to American Joint Committee on Cancer (AJCC) 8th edition,
* Has at least 1 target lesion per RECIST 1.1, as determined by the investigator. Measurable lesions that have been previously irradiated and have been shown to be progressing following irradiation may be considered as TLs.
* Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
* Has a life expectancy of ≥ 3 months with ability to complete at least 4 cycles of study intervention.
* Has adequate organ function
* Is willing to use adequate contraception (contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
* For dose expansion only: Tumor tissue (archival tumor tissue or a fresh biopsy) is required for all participants at screening. Tissue from a newly obtained fresh biopsy is preferred. If it is not feasible to obtain a fresh biopsy at screening, archival tumor tissue, (from the most recent biopsy (within 1 year), Formalin Fixation and Paraffin Embedding FFPE) block (preferred), or freshly cut slides is acceptable. If archival tissue is unavailable and it is not medically feasible to obtain fresh tissue, the medical monitor should be informed and exemption to the tissue requirement may be granted on a case-by-case basis. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression and other biomarker analysis
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to baseline status preceding prior therapy (excluding alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 1 neuropathy).
Has had major surgical procedures or serious trauma within 4 weeks prior to first dose, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator), or minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to first dose.
* Has symptomatic Central Nervous System (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to first dose, potential need for CNS radiation within the first cycle, or leptomeningeal disease. Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent).
* Has any of the following:
* QTc \>450 msec or QTc \>480 msec for participants with bundle branch block.
* Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval \>250 msec).
* Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval.
* Left Ventricular Ejection Fraction (LVEF) \<50%.
* Has severe, uncontrolled or active CV disorders
* Serious or poorly controlled hypertension; adjustment of antihypertensive medications due to poor blood pressure control within 2 weeks prior to the first dose; recurrent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg during screening period.
* History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to first dose, including but not limited to:
* Hemoptysis (defined as coughing up ≥ 1 teaspoon of fresh blood or small blood clots)
* Transient hemoptysis associated with diagnostic bronchoscopy is allowed.
* Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
* Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to first dose is not allowed.
* Participants with a history of esophageal or gastric varicose vein, severe ulcer, unhealed wound, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal hemorrhage within 6 months prior to first dose.
* History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) 6.0, hypertensive crisis, or hypertensive encephalopathy, within 12 months prior to the first dose.
* Serious infections within 4 weeks prior to the first dose, including but not limited to infectious complications, bacteremia, severe pneumonia treated with IV antibiotics for ≥ 2 weeks; active infections with therapeutic IV antibiotics within 2 weeks prior to the first dose or oral antibiotics within 1 week prior to the first dose. Participants who are receiving or have received prophylactic antibiotics (e.g., prophylaxis against urinary infections) are allowed.
* Any evidence of current Interstitial Lung Disease (ILD)/non-infectious pneumonitis OR a prior history of ILD/non-infectious pneumonitis requiring high-dose glucocorticoids OR suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE) and any radiographic features consistent with interstitial lung abnormalities, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
* Participants with moderate to severe pulmonary disease or current clinically significant pulmonary compromise that, in the investigator's judgment, could jeopardize safety or study conduct. Examples include severe/poorly controlled asthma or Chronic Obstructive Pulmonary Disease (COPD) (including acute exacerbation of COPD within 4 weeks before first dose), restrictive lung disease, significant pleural effusion (clinically significant pleural effusion on Study Day 1. Baseline oxygen saturation \< 90% on room air.) or structural lung abnormalities, pulmonary involvement from autoimmune/connective tissue disorders (e.g., rheumatoid arthritis, Sjögren's, sarcoidosis), or any condition requiring continuous supplemental oxygen or causing marked respiratory impairment (e.g., dyspnea at rest, greatly reduced exercise tolerance, or significantly decreased lung function). Treatment of pleural effusions to meet eligibility is permitted.
* History of allergy or hypersensitivity to Ris-Rez (antibody-drug conjugate (ADC), antibody, payload \[GSK5757810\]). History of severe allergies (e.g., anaphylactic shock), or severe infusion-related reactions (IRRs), or idiosyncrasy to recombinant humanized or mouse proteins.
* Has received prior anticancer therapy within 14 days of the first dose of study intervention or having to continue these medications during the study. Participants that had any macromolecular anticancer drug (including immunotherapies such as monoclonal antibodies and bispecific antibodies) within 28 days prior to the first dose of study intervention are excluded.
* History of local radiotherapy within 2 weeks prior to the first dose of study intervention; more than 30% of bone marrow irradiation or extensive radiotherapy within 4 weeks before the first dose of study intervention
* Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), or recombinant erythropoietin) within 14 days before enrollment. G-CSF prophylaxis prior to administration of Ris-Rez is permitted.
* Has received immunosuppressive agents within 30 days prior to first dose of study treatment (or requires long-term (30 days or longer) glucocorticoid therapy). Low-dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered. Use of inhaled or topical steroids and prophylactic corticosteroids for procedures and pre-infusion prophylaxis are permitted.
* Participant with history of nephrotic syndrome or Grade 3 proteinuria or protein urine \>1+ on dipstick or 24-h urine protein quantitation ≥ 1.0 g at Screening.
* History of abdominal or gastrointestinal fistula, tracheoesophageal fistula or any Grade 4 fistula, gastrointestinal perforation, or intra-abdominal abscess.
* Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety). Renal obstruction successfully managed by stenting is permitted.
A Study to Assess Safety and Efficacy of SOT109 in Patients With Advanced Unresectable or Metastatic Colorectal Cancer
SOT109, a CDH17-directed antibody-drug conjugate carrying the topoisomerase inhibitor payload exatecan, is being studied in patients with previously treated advanced unresectable or metastatic colorectal cancer.
NCT07693751 · Phase 1/2 · SOTIO Biotech a.s.
Recruiting sites: Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. ≥18 years of age on the day of signing the ICF
2. Able to understand, sign, and provide written informed consent to participate in the trial
3. Performance status: Eastern Cooperative Oncology Group (ECOG) performance score 0-1. Patients with ECOG performance score 2 will be discussed with the sponsor's medical monitor to be agreed for inclusion
4. Estimated life expectancy ≥3 months as assessed by the investigator
5. An appropriate candidate for experimental therapy as assessed by the investigator
6. Agrees not to participate in other interventional clinical trial while enrolled in the present trial (with the exception of survival follow-up period)
7. Absolute neutrophil count ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥9 g/dL
8. Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula
9. Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in case of liver involvement: AST and ALT ≤5×ULN
• Participants with a documented history of Gilbert syndrome may be eligible if:
* Total bilirubin is ≤2.0 × ULN,
* Direct (conjugated) bilirubin is within normal limits (≤ULN), and
* There is no evidence of active liver disease, clinically significant hepatic impairment, hemolysis, or biliary obstruction, as determined by the investigator
10. Prothrombin time/international normalized ratio ≤1.5×ULN
11. Albumin ≥3.0 mg/dL
12. Serum concentrations of potassium, magnesium, and calcium with abnormalities of maximum grade 1 that should be treated according to standard practice
13. Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography or nuclear medicine methodology (MUGA)
14. QTcF interval ≤470 msec on screening ECG
15. Histological or cytological evidence of advanced unresectable or metastatic colorectal cancer
16. Participants that received and progressed on standard systemic therapies (fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and, only when locally indicated and available, a BRAF/RAS/HER2 inhibitor) and who have no further standard treatment options. Participants with a known microsatellite instability-high (MSI-H) status must have received treatment with an immune checkpoint inhibitor (if locally indicated and available) unless contraindicated
17. Measurable or non-measurable disease according to RECIST 1.1
18. Previous cancer therapies:
18.1. Europe: previous cancer therapies and any agents that have not received regulatory approval for any indication must have been discontinued either ≥21 days prior to day 1 of cycle 1 or ≥5x half-life, whichever is longer; toxicities of earlier anticancer therapy must be grade ≤1 at the time of screening and prior to cycle 1 day 1 (exception: alopecia) 18.2. US: eligibility should be determined based on patient recovery from clinically significant adverse events from their most recent therapy or intervention prior to study enrollment
19. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: 19.1. Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche, and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient.
19.2. A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 6 months after the last dose of SOT109
* WOCBP can only be included after a negative serum pregnancy test at screening
* Highly effective contraception includes:
* Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation:
* Oral
* Intravaginal
* Transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation:
* Oral
* Injectable
* Implantable
* Intrauterine device
* Intrauterine hormone-releasing system
* Bilateral tubal occlusion
* Vasectomized partner provided the partner is the sole sexual partner of the WOCBP participant and that the vasectomized partner has received medical assessment of the surgical success
* Sexual abstinence defined as refraining from heterosexual intercourse during the entire treatment period and for at least 6 months after the last dose of SOT109. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
20. Male participants must agree to use a condom during the treatment period and for at least 6 months after the last dose of SOT109. Male participants wishing to become a father during or after the trial should consider sperm preservation. WOCBP partners of male participants should use highly effective contraception methods for 6 months after SOT109 discontinuation.
Exclusion Criteria:
1. Received radiation therapy ≤14 days before day 1 of cycle 1 or not recovered to grade ≤1 from treatment-related side effects
2. Any prior systemic therapy for metastatic cancer other than colorectal cancer; exception:
stable disease under hormonal treatment for prostate cancer, stable disease under hormonal treatment for breast cancer; radiochemotherapy is allowed if such treatment is completed at least 4 weeks prior to day 1 of cycle 1; participants must have recovered to grade ≤1 from all side effects (exception: alopecia)
3. Participants must not receive any concurrent antitumor therapy while participating in the trial. In exceptional circumstances where urgent palliative radiotherapy to symptomatic non-target lesions is clinically indicated, the case must be reviewed with the Principal Investigator (PI) and the intervention must receive prior approval from the sponsor
4. Vaccination with a live or live-attenuated vaccine within 30 days prior to the first dose of trial interventions; the full series (e.g., both doses of a two dose vaccination series) should be completed prior to dosing if feasible
5. Time since last transfusion of red blood cells ≤14 days before day 1 of cycle 1
6. Severe preexisting medical conditions as per judgment of the investigator
7. History of interstitial pneumonitis or pulmonary fibrosis
8. Symptomatic central nervous system malignancy. Participants with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days
9. Peripheral sensory neuropathy grade ≥2
10. Active infection requiring systemic therapy that is not clinically controlled before the signature of the ICF
11. Known symptomatic HIV positive, symptomatic active HBV, or symptomatic active HCV
Note:
* Participants with HIV will be eligible if:
* CD4+ T-cell counts ≥350 cells/μL
* They have no history of AIDS-defining opportunistic infections
* They are not currently on HIV therapy
* Participants with HBV will be eligible if there is serologic evidence of a resolved prior HBV infection (HBsAg-negative and HBcAb-positive)
* Participants with HCV will be eligible if they have completed curative antiviral treatment and have HCV viral load below the limit of quantification 12. Alcohol or drug abuse as determined by the investigator 13. Psychiatric condition or social situation that, in the opinion of the investigator, preclude that the participant is able to comply with trial requirements 14. New York Heart Association class ≥2 heart failure, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, myocardial infarction, cerebrovascular accident or hypertensive crisis within 6 months prior to day 1 of cycle 1 15. History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes) 16. History or family history of congenital long QT syndrome 17. Bradycardia (\<50 beats per minute) 18. Family history of sudden cardiac death before age 50 19. Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention 20. Hypersensitivity or intolerance to any component of trial intervention 21. Medical history of inflammatory bowel disease or active inflammatory bowel disease (IBD)
* Participants with signs or symptoms suggestive of IBD who have not undergone colonoscopy to rule out IBD will be excluded
Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
Autologous B7-H3-targeted CAR T cell therapy, given after cyclophosphamide/fludarabine lymphodepletion, is being studied in previously treated recurrent or refractory extensive-stage small cell lung cancer and extrapulmonary neuroendocrine carcinoma.
NCT07509034 · Phase 1 · National Cancer Institute (NCI)
Recruiting sites: Maryland
Read full eligibility criteria
* INCLUSION CRITERIA:
* Age \>=18 years old.
* Histologically confirmed small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that has recurred following or is refractory to first-line therapy. Note: small cell cancers of non-lung primary sites are also eligible.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
* Pulse oximetry \>= 90% on room air.
* Aspartate Transferase (AST) \< 3 X institutional upper limit of normal (ULN). Note: in case of liver metastases \<= 5 X ULN is acceptable.
* Alanine Aminotransferase (ALT) \< 3 X institutional ULN. Note: in case of liver metastases \<= 5 X ULN is acceptable.
* Total bilirubin \<=2 X institutional ULN.
* Creatinine \<=1.5 X institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min/1.73m\^2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula or calculated eGFR provided by a laboratory).
* Absolute Neutrophil Count (ANC) \>= 750/mcL.
* Platelet count \>= 75,000/mcL.
* An absolute lymphocyte count (ALC) \>=300/mcL and CD3+ cell count \>=150/mcL.
* Normal cardiac ejection fraction as defined by \>= 45% by echocardiogram (ECHO) at screening.
* At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 that has not been previously irradiated.
* Recovered from acute toxic effects of all prior cancer therapy to Grade \<2 per Common Terminology Criteria for Adverse Events (CTCAE) v.6.0 at least one week before apheresis excluding the parameters for ANC and ALC mentioned above.
* The following criteria must be met prior to apheresis:
* Chemotherapy and biologic/targeted agents:
* \>=14 days since the last dose of standard myelosuppressive chemotherapy.
* \>= 7 days since the completion of biologic agent, targeted agent, or tyrosine kinase inhibitor therapy.
* \>= 3 weeks or 5 half-lives (whichever is shorter) since prior therapy with a monoclonal antibody.
* Radiotherapy:
* \>= 1 week since the last radiotherapy session.
* No washout period required for palliative radiation to non-target lesions.
* \>= 3 weeks since hepatic radiation, chemoembolization, and/or radiofrequency ablation.
* Steroids and immunosuppressive therapy:
* Corticosteroids: \>= 2 weeks since the therapeutic doses (\> 0.5 mg/kg/day prednisone or equivalent). Note: Inhaled or topical steroids are not exclusionary.
* Physiologic replacement doses (up to 5 mg/day prednisone equivalent) are allowed and can be adjusted based on participant's BMI if warranted.
* \>= 2 weeks since the other immunosuppressive medication (e.g., calcineurin inhibitors, methotrexate, rapamycin, thalidomide, etc.).
* Anti-PD-1 and any investigational therapies:
* \>= 2 weeks since Anti-PD-1 monoclonal antibody therapy.
* \>= 2 weeks or 5 half-lives of the investigational product (whichever is shorter) since any investigational treatment or clinical trial participation.
* Other criteria:
* 72 hours since small molecule tyrosine kinase inhibitors (e.g., EGFR inhibitors), PARP inhibitors, or KRAS G12C inhibitors.
* Individuals of childbearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy.
Note: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.
* Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 7 months after the last dose of study drugs. We also will recommend individuals able to father a child with partners of childbearing potential ask partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period.
* Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s).
* Ability of the participant to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
* History of anaphylactic reactions attributed to anti-B7-H3 antibodies or compounds of similar chemical or biologic composition to autologous B7-H3 CAR T cells, cyclophosphamide, fludarabine, or other agents used in this study.
* Infection exposure with the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as defined below:
* Positive serology for HIV.
* Active HBV infection as demonstrated by test for hepatitis B surface antigen (HBsAg).
* Positive serology for HCV.
* Prior gene therapy using an integrating vector (except for autologous B7-H3 CAR T cells retreatment).
* History of any previous allogeneic hematopoietic stem cell transplant.
* Presence of fungal, bacterial, viral, or other infection is permitted if responding to active treatment.
* Central Nervous System (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that may impair the ability to evaluate neurotoxicity.
* Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP at screening.
* Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history, physical exam, electrocardiogram (ECG) or situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.
Comparing the Effectiveness of Less Invasive Procedures With the Current Standard of Care for the Treatment of Older Adults With Early-Stage Melanoma
This trial compares wide local excision alone versus wide local excision plus sentinel lymph node biopsy (standard of care) as surgical treatment for older adults (≥75 years) with newly diagnosed early-stage cutaneous melanoma.
NCT07068074 · Phase 3 · ECOG-ACRIN Cancer Research Group
Recruiting sites: Alabama, Alaska, Arizona, California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Kansas, Kentucky, Louisiana, Maryland, Michigan, Minnesota, Missouri, Montana, Nebraska, Nevada, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Vermont, Virginia, Washington, West Virginia, Wisconsin, Wyoming
Read full eligibility criteria
Inclusion Criteria:
* Patient must be ≥ 75 years of age.
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
* Patient must have newly diagnosed primary cutaneous melanoma with wide local excision (WLE) and sentinel lymph node (SLN) biopsy indicated per the treating physician, pending definitive surgical management.
* NOTE: For WLE and SLN to be indicated, the patient must have either:
* Pathologic features that include ≧ Breslow 0.8 mm OR Breslow \< 0.8 mm determined at initial biopsy, with a positive margin, ulceration, lymphovascular invasion, perineural invasion or \> 1 mitosis/mm\^2.
OR
* Risk of SLN metastasis of at least 5%, as calculated using the Melanoma Institute of Australia (MIA) Sentinel Node Metastasis Prediction Tool.
* Patient must be eligible for WLE and SLN biopsy. Patients for whom SLN biopsy would be contraindicated, difficult to perform (i.e., after prior surgery in the draining basin) or impossible (i.e., after prior lymphadenectomy for another cause) are not eligible.
* Patient must be eligible for surgery and not have uncontrolled medical condition that in the opinion of the medical or surgical oncologist precludes surgical management.
* Patient must not have an active infection that precludes enrollment to this study in opinion of treating investigator.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better.
* Patient must be English speaking to be eligible for this study in order to complete the patient-reported outcomes (PROs).
* NOTE: Sites cannot translate the associated quality of life (QOL) forms.
JUR-003 in Adult Patients With Metastatic Prostate Cancer
JUR-003, an intravenously administered biological agent whose specific mechanism is not stated in the registry, is being studied in a first-in-human Phase 1a/1b trial in patients with metastatic prostate cancer (including CRPC, oligometastatic, and hormone-sensitive disease).
NCT07824349 · Phase 1 · Juri Biosciences, Inc.
Recruiting sites: Michigan, New York, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria:
* Must be ≥18 years of age at the time the informed consent form (ICF) is signed.
* Has a histologically or cytologically confirmed adenocarcinoma of the prostate.
* Has either of the following:
1. Measurable disease per RECIST v1.1 (with PCWG3 modifications)
2. Evaluable disease per PCWG4, as assessed by the local site Investigator/radiology
3. For Part 2.1B (omPC expansion) only: PSMA-avid disease on PSMA-PET, defined as lesion(s) demonstrating uptake above blood pool (PSMA score ≥1) and assessed by the Investigator as consistent with metastatic prostate cancer, in the setting of biochemical recurrence (PSA ≥0.2 ng/mL).
Exclusion Criteria:
* Has a diagnosis of immunodeficiency.
* Has had a prior stem cell, bone marrow, or organ transplant.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has active or chronic hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
* Has an active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* Has a history of (noninfectious) pneumonitis that required steroids or current active organizing pneumonitis/interstitial lung disease.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals with previously treated CNS metastases may participate in JUR-003 monotherapy cohorts (Parts 1.1, 2.1, and 1.3 where applicable) provided they are radiologically stable (ie, without evidence of progression for at least 2 weeks by repeat imaging \[note that the repeat imaging should be performed during study Screening\]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study drug.
* Has untreated spinal cord compression. Individuals must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug.
* Has a history of a previous secondary malignancy within 3 years of Screening (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative therapy or other localized, low-grade tumors deemed cured, or whose natural history does not have the potential to interfere with the safety or efficacy assessments of the current study and not treated with systemic anticancer therapy \[except hormonal therapy\]).
* Has a known psychiatric or substance abuse disorder that would interfere with the individuals' ability to cooperate with the requirements of the study.
* Has a history of venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to the first dose of JUR-003. Uncomplicated (Grade ≤2) deep vein thrombosis is not considered exclusionary.
PSMA-High: EBRT/ PSMA617/ ADT vs. EBRT/ ADT
This phase 2 trial compares EBRT plus ADT with or without 177Lu-PSMA-617 (a PSMA-targeted radioligand therapy) using a shortened 6-month ADT course, in men with high-risk localized prostate cancer undergoing definitive treatment.
NCT07550517 · Phase 2 · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting sites: Maryland
Read full eligibility criteria
Inclusion Criteria:
* Patient must have high-risk prostate cancer (HRPC) defined by presence of exactly one high-risk feature: cT3a OR Grade Group 4 or 5 OR PSA \> 20 ng/mL.
* Histologic confirmation of adenocarcinoma of the prostate.
* Patient must have localized HRPC defined by conventional imaging (no N1 disease by CT or MRI). Patients with or without intra-pelvic nodal metastases by PSMA-PET may be included as long as not enlarged \>10mm short axis by conventional CT size criteria.
* Patients must have PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL) with prostate tumor SUVmax \> 10.
* Patient must qualify for definitive treatment of prostate cancer including EBRT as well as ADT (up to 45 days of prior ADT is allotted).
* Patient must be ≥ 18 years of age.
* Patient must have a life expectancy ≥ 24 months.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 6 weeks demonstrating:
1. Platelet count of \>100 x109/L
2. White blood cell (WBC) count \> 3,000/mL
3. Neutrophil count of \> 1,500/mL
4. Hemoglobin ≥ 10 g/dL
5. Estimated glomerular filtration rate (eGFR) \> 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA-617, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
6. Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)
7. Serum albumin \> 30 g/L
8. Aspartate aminotransferase (AST) \< 3 times the ULN
* For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA-617.
* Patient must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Presence of a very high-risk feature: cT3b to T4 OR primary pattern 5 OR 2 to 3 high-risk features OR \>4 cores with Grade Group 4 or 5.
* Any prior pharmacotherapy (with the exception of up to 45 days of ADT prior to randomization), radiation therapy, or surgery as treatment for prostate cancer. Any prior radiopharmaceutical therapy.
* Any prior radiation to the pelvis.
* Presence of N1 or M1 disease by conventional imaging (CT, MRI, and/or bone scan) or M1 disease by PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL). Lymph nodes with short axis \> 8 mm by CT will be considered N1 by conventional imaging.
* Castration-resistant prostate cancer (CRPC).
* Patient receiving any other investigational agents.
* Patient is participating in a concurrent treatment protocol involving radiotherapy, surgery, or systemic anti-cancer agents.
* Inadequate bone marrow reserve and organ function as detailed in 5.1.10.
* Unable to lie flat during or tolerate PET/MRI, PET/CT or EBRT.
* Concurrent serious medical condition that, in the opinion of the Investigator, would impair study participation.
* Contraindication to receiving pelvic radiation, including history of or active inflammatory bowel disorders.
* Refusal to sign informed consent.
Sacituzumab Govitecan With Bevacizumab Compared to Usual Chemotherapy (Carboplatin, Pegylated Liposomal Doxorubicin and Bevacizumab) for Treating Recurrent Platinum-Sensitive Ovarian Cancer After PARP Inhibitor Maintenance Therapy
Sacituzumab govitecan (a TROP2-directed antibody-drug conjugate delivering SN-38) plus bevacizumab (anti-VEGF monoclonal antibody) is compared to standard carboplatin/pegylated liposomal doxorubicin/bevacizumab chemotherapy in patients with recurrent platinum-sensitive, BRCA-mutated or homologous recombination deficient ovarian/fallopian tube/primary peritoneal cancer that progressed after first-line PARP inhibitor maintenance.
NCT07504588 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: Arkansas, Idaho, Iowa, Missouri, Montana
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologic diagnosis of high grade serous or endometrioid epithelial ovarian cancer
* Ovarian cancer = fallopian tube, ovarian, and primary peritoneal cancer
* Disease must be platinum sensitive, as defined by progression documented ≥ 6 months (182 days) from the last receipt of platinum
* Disease must have progressed during first line maintenance PARP inhibitor (PARPi) for advanced ovarian cancer. NO intervening therapies between progression on PARPi and study registration are permitted
* Disease must be germline or somatic BRCA1 or BRCA2 mutated or homologous recombination deficiency test positive
* Disease must be measurable or non-measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1
* Secondary or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted
* No previous receipt of any topoisomerase-I inhibiting agents
* No investigational agents within 4 weeks of study registration
* No current treatment with any other (non-study) cytotoxic chemotherapy, targeted therapy, biologic therapy, immunotherapy or endocrine therapy for the treatment of the disease under the current study
* Last dose of PARP inhibitor treatment must be ≥ 3 weeks before study registration
* Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after CNS-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 9 g/dl is acceptable)
* Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
* Urinalysis with ≤ 1+ protein and/or urine protein \< 1.0 g/24 hours (hrs)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parenteral antibiotics
* No non-healing wound, ulcer, or bone fracture
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No clinically significant bleeding within 28 days prior to registration
* No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the following exceptions:
* Patients with grade 2 or lower neuropathy, any grade alopecia, well controlled hypertension, thyroid disease controlled with therapy, and history of thromboembolic disease on anticoagulation are eligible
* Patients with laboratory-based grade 2 or higher adverse events (AEs) that meet the criteria outlined above are eligible
* No major surgery within 3 weeks prior to study registration
* Patients who underwent major surgery must have recovered adequately from any toxicity and/or complications from surgery prior to study registration
* No strong inhibitors or inducers of UGT1A1
* No history of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer
HTR2 T cells, HER2-targeted CAR T cells co-engineered with an anti-TRAIL-R2 antibody component and IL-15, are being studied for safety and dosing in HER2-positive metastatic or locally recurrent unresectable breast cancer that progressed after first-line therapy.
NCT06251544 · Phase 1 · Baylor College of Medicine
Recruiting sites: Texas
Read full eligibility criteria
Procurement Inclusion Criteria:
1. Any patient between 18-80 years of age regardless of sex, with a diagnosis of metastatic or locally recurrent unresectable HER2 positive breast cancer.
2. HER2 tumor expression1+, 2+ or 3+ by IHC
3. The disease must have progressed after standard first line therapy. Patients are still eligible if they have failed more than one line of therapy.
4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Treatment Inclusion Criteria:
1. Patients between ages 18 and 80 years old with a diagnosis of either stage IV breast cancer or locally recurrent unresectable breast cancer. Disease must have progressed after standard first line therapy. Patients are still eligible if they have failed more than one line of therapy.
2. Measurable or evaluable disease per RECIST 1.1 criteria.
3. HER2 tumor expression 1+, 2+ or 3+ by IHC.
4. Bilirubin ≤ 3x upper limit of normal.
5. AST and ALT ≤ 3x upper limit of normal
6. Hemoglobin ≥ 7 g/dl (may be transfused values)
7. Serum creatinine \< 2 x the upper limit of normal.
8. Pulse oximetry of \> 90% on room air.
9. Off conventional or investigational therapy for 3 weeks prior to study entry.
10. ECOG Performance Status ≤ 2
11. The patient is able to understand and give informed consent to study related procedures and treatments.
Procurement Exclusion Criteria:
1. Known pregnancy or actively breast feeding.
2. Active and uncontrolled bacterial, viral, or fungal infection.
3. Patients with current use of systemic corticosteroids (Prednisone equivalent \>0.5mg/kg/day).
4. Patients with abnormal left ventricular function (LVEF \<55%)
5. Patients with brain metastases that are progressing.
Treatment Exclusion Criteria:
1. Pregnant or breast feeding
2. Active and uncontrolled bacterial, viral or fungal infection
3. Patient with current use of systemic corticosteroids (prednisone equivalent \>0.5 mg/kg/day.
4. Patients with abnormal left ventricular function (LVEF \<55%).
5. Patients with brain metastases that are progressing
Testing the Combination of Anti-Cancer Drugs, Selumetinib and DS-8201a (Trastuzumab Deruxtecan), for Advanced Pancreatic Ductal Adenocarcinoma
This phase I/II trial tests the combination of selumetinib, a MEK1/2 inhibitor, plus trastuzumab deruxtecan, a HER2-targeted antibody-drug conjugate, in patients with advanced, unresectable, or metastatic pancreatic ductal adenocarcinoma with KRAS mutation and HER2 positivity after prior systemic chemotherapy.
NCT07619521 · Phase 1/2 · National Cancer Institute (NCI)
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
* Review of eligibility criteria by the study principal investigator (PI) is required prior to enrollment
* Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
* Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2 immunohistochemistry (IHC) positivity (2+ or above for dose escalation and per decision rule for phase II), as determined by a Clinical Laboratory Improvement Act (CLIA)-certified kit using gastric cancer criteria
* Patients must have measurable disease that can fulfill Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
* Patients must have exposure to at least one line of systemic chemotherapy for metastatic or unresectable PDAC (for both escalation and phase II cohorts) or a documented patient decision to forego therapy that has an otherwise proven survival advantage (for escalation cohort only)
* Patients who have received prior topoisomerase inhibitors including irinotecan and nanoliposomal irinotecan will be eligible for this study
* Only 1 prior line of therapy for metastatic or unresectable PDAC will be allowed for patients in the phase II cohort. Adjuvant or neoadjuvant therapy does not count, assuming it was completed \> 6 months prior to the start of systemic therapy for metastatic or unresectable disease
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of selumetinib (AZD6244 hydrogen sulfate) in combination with DS-8201a (trastuzumab deruxtecan) in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 70%). Regardless of performance status, enrollment should be based on the judgment of the treating physician that the patient will be able to be safely treated with the proposed therapeutic intervention
* Hemoglobin ≥ 9 g/dL (within 14 days of enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Leukocytes ≥ 3,000/mcL (within 14 days of enrollment)
* Absolute neutrophil count ≥ 1,500/mcL (within 14 days of enrollment)
* No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
* Platelets ≥ 100,000/mcL (within 14 days of enrollment)
* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (\< 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14 days of enrollment)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 5 × ULN in participants with liver metastases (within 14 days of enrollment)
* Serum albumin ≥ 2.5 g/dL (within 14 days of enrollment)
* International Normalized Ratio (INR)/Prothrombin Time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (within 14 days of enrollment)
* Creatine phosphokinase (CPK) ≤ 2.5 × ULN (within 14 days of enrollment)
* Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 (within 14 days of enrollment)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging, performed at least 6 months after central nervous system (CNS)-directed therapy, shows no evidence of progression
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must undergo a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible, patients must be NYHA Class II or better and have no history of myocardial infarction within 6 months prior to enrollment, no symptomatic congestive heart failure (NYHA Class IIb-IV), and no troponin levels consistent with myocardial infarction (as defined by the manufacturer) within 28 days prior to enrollment
* Patients must have a baseline left ventricular ejection fraction (LVEF) ≥ 50% as measured by echocardiogram (ECHO) or mutilated acquisition scan (MUGA) scan within 28 days before randomization/enrollment
* Patients must be willing to undergo baseline ophthalmic evaluation, including visual acuity and slit-lamp examination
* The effects of selumetinib (AZD6244 hydrogen sulfate) and DS-8201a (trastuzumab deruxtecan) on the developing human fetus are unknown. For this reason and because MEK inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months (for WOCBP) or 4 months (for men) after completion of drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Patients with prior MEK inhibitor, ERK inhibitor, or HER2-directed therapy treatment
* Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents), weekly paclitaxel; 6 weeks for nitrosoureas or mitomycin C
* Patients who have had immunotherapy including monoclonal antibody therapy within 4 weeks
* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
* Patients who have had a major surgery within 4 weeks
* Patients with a history of allogeneic organ or stem cell transplant
* Patients who are receiving any other investigational agents or received any other investigational agents within the past 21 days prior to protocol treatment initiation
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib (ADZ6244 hydrogen sulfate) or DS-8201a (trastuzumab deruxtecan)
* Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment
* Patients with prior use of immunosuppressive medication within 14 days prior to first study dose, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses less than 10 mg/day of prednisone or equivalent
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Patients with a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
* Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, presence of ILD that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity, or where suspected ILD cannot be ruled out by imaging at screening. These patients will be excluded because DS-8201a (trastuzumab deruxtecan) is known to increase the risk of developing ILD and pneumonitis
* Patients with lung-specific, intercurrent, clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months prior to study enrollment, severe asthma, severe chronic obstructive pulmonary disorder (COPD), restrictive lung disease, significant pleural effusion, etc.), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), and/or prior pneumonectomy. These patients will be excluded because DS-8201a is known to increase the risk of developing ILD and pneumonitis
* Patients with gastrointestinal conditions which could impair absorption of selumetinib (AZD6244 hydrogen sulfate) or inability to ingest selumetinib (AZD6244 hydrogen sulfate)
* Patients with a history of significant retinal pathology (including but not limited to, retinal vein occlusion, retinal detachment, or macular degeneration) or clinically significant ophthalmic abnormalities that may increase the risk of retinal adverse events
* Active ocular disease requiring systemic therapy or current use of contact lenses that may interfere with ophthalmic evaluations
* Based on pre-clinical and clinical data, DS-8201a (trastuzumab deruxtecan) and selumetinib (AZD6244 hydrogen sulfate) are associated with ocular toxicity. Patients with clinically significant corneal disease, in the opinion of the investigator, will be excluded from this study
* Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic body radiation therapy). These patients will be excluded because DS-8201a (trastuzumab deruxtecan) is known to increase the risk of developing pneumonitis
* Patients with spinal cord compression, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Patients that have received a live vaccine within 30 days prior to the first dose of study drug will be excluded. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed
* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia or peripheral neuropathy) not yet resolved to grade ≤ 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy). Subjects should no longer be symptomatic nor require treatment with corticosteroids or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy
* Patients with ongoing muscle disorders or elevated baseline creatine phosphokinase (CPK) levels suggestive of rhabdomyolysis or myopathy
* Patients currently using high-dose vitamin E supplements exceeding the recommended daily intake (≥ 400 IU/day) or concurrent use of anticoagulants/antiplatelets that may increase bleeding risk, unless clinically indicated and closely monitored
* Pregnant women are excluded from this study because selumetinib (AZD6244 hydrogen sulfate) is a MEK inhibitor agent with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selumetinib (AZD6244 hydrogen sulfate) breastfeeding should be discontinued if the mother is treated with selumetinib (AZD6244 hydrogen sulfate). These potential risks also apply to treatment with DS-8201a (trastuzumab deruxtecan)
* Patients who have received prior systemic anticancer therapy, investigational agents, or radiotherapy without completion of an adequate washout period prior to study treatment initiation defined as at least 14 days or \> 5 half-lives of the prior agent (whichever is shorter). This applies to therapies with potential overlapping toxicities with DS-8201a (trastuzumab deruxtecan) or selumetinib (AZD6244 hydrogen sulfate) including but not limited to agents associated with pulmonary toxicity, cytopenias, or gastrointestinal toxicity
Zanzalintinib Alone or in Combination With Pembrolizumab and Berahyaluronidase Alfa in Participants With Colorectal Cancer With Molecular Residual Disease
This phase 3 trial tests zanzalintinib, an oral multi-kinase (c-Met/VEGFR2/AXL/MER) inhibitor, alone or combined with the PD-1 inhibitor pembrolizumab (co-formulated with berahyaluronidase alfa), versus placebo in patients with stage II/III colorectal cancer who have molecular residual disease (ctDNA-positive) after completion of definitive therapy.
NCT07750158 · Phase 3 · Exelixis
Recruiting sites: Iowa, Nebraska, New Jersey
Read full eligibility criteria
Key Inclusion Criteria:
* Histologically confirmed diagnosis of Stage II or III adenocarcinoma of colon or rectum.
* Documented local MSI and/or mismatch repair (MMR) test result demonstrating MSS, MSI-low, or pMMR status.
* Colon or rectal cancer with completed definitive therapy.
* ctDNA-positive based on local testing using the Natera Signatera tissue-informed molecular residual disease (MRD) assay.
* No radiographic evidence of disease, as confirmed by a negative baseline computed tomography (CT) of the chest, abdomen, and pelvis (CAP), or CT of chest and magnetic resonance imaging (MRI) of abdomen/pelvis.
Key Exclusion Criteria:
* History of solid organ or allogeneic stem cell transplant.
* Known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Prior treatment with immune checkpoint inhibitors (ICIs) or Vascular endothelial growth factor receptor (VEGFR) inhibitors.
* History of CRC requiring systemic anticancer therapy prior to the definitive therapy.
* Use of systemic anticancer therapy (including investigational therapy) or radiation therapy after the completion of definitive therapy.
* Administration of a live, attenuated vaccine within 30 days of randomization and during treatment.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
AQUA07 in Patients With ALK-Positive Non-Small Cell Lung Cancer
AQUA07, an oral agent whose mechanism is not stated in the registry, is being studied as monotherapy and in combination with the ALK/ROS1 inhibitor lorlatinib in patients with previously ALK-TKI-treated, locally advanced or metastatic ALK-positive NSCLC.
NCT07617337 · Phase 1 · Chugai Pharmaceutical
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
* Age ≥ 18 years (or ≥ 20 years if required by local regulation) at time of signing Informed Consent Form
* Previously treated with at least one ALK-TKI regardless of prior chemotherapy treatment (Patients who have received only crizotinib as prior ALK-TKI treatment will not be allowed.)
* Histologically or cytologically (excluding sputum cytology) proven diagnosis of locally advanced unresectable or metastatic ALK-positive NSCLC, who have experienced disease progression during or following their most recent systemic therapy or have discontinued the therapy due to unacceptable toxicity
* Measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Ability and willingness to take oral medication(s)
* Adequate organ function and bone marrow reserve
Exclusion Criteria:
* Prior toxicities from anti-cancer therapy which have not resolved to Grade ≤ 1 per NCI CTCAE v5.0 excluding alopecia, vitiligo, or endocrinopathies manageable with replacement therapy
* Symptomatic, active CNS metastases or untreated CNS metastases requiring any definitive therapy.
* Severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or renal disease, or active infection), or with a history or complication of interstitial lung disease
* Significant cardiovascular disease
* Inadequately controlled hypertension
* (Part B only) Patients with prior lorlatinib treatment who experienced serious lorlatinib-related toxicities, or who experienced toxicities considered inappropriate for study participation at the discretion of the Investigator
GLP-1 RA Plus SOC Treatment in First-line, Metastatic Pancreatic, Colorectal, or Hepatocellular Cancer
This early-phase trial adds semaglutide, a GLP-1 receptor agonist, to standard first-line chemotherapy regimens in patients with metastatic pancreatic, colorectal, or hepatocellular cancer to assess safety and tolerability.
NCT07627191 · Phase 1 · University of Arizona
Recruiting sites: Arizona
Read full eligibility criteria
Inclusion Criteria:
* Histological or cytological diagnosis of pancreatic adenocarcinoma or colorectal adenocarcinoma. Previous tumor tissue testing is acceptable. Please refer to the "additional HCC cohort criteria" below.
* The subject has disease that is not amenable to curative-intent management (e.g., oligometastatic disease)
* Measurable disease per RECIST v1.1 as determined by the investigator
* Patients must be appropriate candidates for first-line, SOC treatment.
* SOC treatment as defined by NCCN® guidelines or institutional standard is allowable, however, options restricted to:
* Colorectal: FOLFOX or FOLIFIRI +/- bevacizumab
* Pancreatic: mFOLFIRINOX
* HCC: Tremelimumab/Durvalumab
* Patients are eligible who received prior perioperative chemotherapy for curative intent treatment and recurred ≥ 6 months since last dose of chemotherapy.
* ≥ 18 years old on day of consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate archival frozen or fixed tissue available from primary or metastatic site for genotypic analysis (at least 15 unstained slides and/or tumor block)
* Adequate hematologic and organ function laboratory values as follows:
* The ANC ≥ 1500/mm3 without colony stimulating factor support;
* Platelets ≥ 75,000/mm3;
* Hemoglobin ≥ 9 g/dL;
* Bilirubin ≤ 1.5 ´ the ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL;
* Serum albumin ≥ 2.8 g/dl;
* ALT and AST ≤ 3.0 ´ ULN;
* Serum creatinine ≤ 1.5 ´ ULN or creatinine clearance (CrCl) ≥ 40 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:
* Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72);
* Female: Multiply above result by 0.85;
* The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
* Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control or practice abstinence during the study and for 4 months after the last dose of study drug(s);
Additional Inclusion Criteria for HCC Cohort ONLY:
* Histologically or radiologically confirmed hepatocellular carcinoma (per AASLD/EASL criteria)
* Unresectable or advanced HCC not amenable to curative surgery or locoregional therapy.
* Barcelona Clinic Liver Cancer (BCLC) stage B or C.
* Child-Pugh Score Class A; or Child-Pugh Class B7 or B8 at discretion of treating physician
* Patients with HBV infection, characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV deoxyribonucleic acid (DNA) (≥10 IU/mL or above the limit of detection per local or central lab standard), must be treated with antiviral therapy, as per institutional practice to ensure adequate viral suppression (HBV DNA \<2000 IU/mL) before enrolment. Patients must remain on antiviral therapy for the duration of their participation in the EAP and for 6 months after the last dose of EAP medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/mL or under the limit of detection per local or central lab standard) do not require anti-viral therapy before enrolment. These participants will be tested at every cycle to monitor HBV DNA levels and initiate anti-viral therapy if HBV DNA is detected (≥10 IU/mL or above the limit of detection per local or central lab standard). HBV DNA detectable patients must initiate and remain on anti-viral therapy for time they are on the EAP and for 6 months after the last dose of EAP medication.
o Note: Testing required for subjects with a known history otherwise not required.
* Patients with HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrolment (management of this disease is per local institutional practice).
Exclusion Criteria
* The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) for metastatic and/or unresectable disease.
* BMI \< 25 kg/m2
* For colorectal cancer only - Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) tumors.
* For colorectal cancer only - BRAF V600E mutant tumors.
* A personal or family history of medullary thyroid cancer (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
* A prior hypersensitivity reaction to semaglutide or any of the excipients in WEGOVY®. Serious hypersensitivity reaction, including anaphylaxis and angioedema, have been reported with WEGOVY®.
* Cachexia
* Subjects on insulin.
* Subjects with a history of diabetic retinopathy
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
o Cardiovascular disorders including:
* For patients being considered for bevacizumab (or bevacizumab biosimilar) only:
* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
* thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (eg, vena cava filter) within 6 months before the first dose of study treatment.
* Any of the following within 6 months before the first dose of study treatment:
* unstable angina pectoris;
* clinically-significant cardiac arrhythmias;
* stroke (including transient ischemic attack (TIA), or other ischemic event);
* myocardial infarction;
* GI disorders particularly those associated with a high risk of perforation or fistula formation including:
* Unresolved abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess.
* Uncontrolled nausea, vomiting, or abdominal pain.
* Other clinically significant disorders that would preclude safe study participation
* Major surgery within 8 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
* Females who are known or suspected to be pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test result within screening.
* Female patients planning on becoming pregnant while on study.
* Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment.
* Male subjects unwilling to abstain from donating sperm during treatment.
* Inability to comply with self-administration of GLP-1 RA subcutaneous injections.
* Subject has known sensitivity to any of the products or components to be administered during dosing.
* Concurrent use of other semaglutide containing products or any other GLP-1 receptor agonist.
* Diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
* Subject likely to not be available to complete all protocol-required study visits or procedures and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
* History or evidence of any other clinically significant disorder, condition or disease that in the opinion of the investigator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Additional Exclusion Criteria for HCC Cohort ONLY:
* Child-Pugh Score Class B9; or Child-Pugh Class C
* Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of EAP treatments.
* History of allogenic organ transplantation (e.g., liver transplant).
* History of hepatic encephalopathy within the past 12 months or requirement for medications to prevent or control encephalopathy (e.g., no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy.
* Clinically meaningful ascites, defined as any ascites requiring non-pharmacologic intervention (e.g., paracentesis) to maintain symptomatic control, within 2 months before the first EAP treatment dose. Patients on stable doses of diuretics for ascites for ≥2 months are eligible.
* Patients with main portal vein thrombosis (i.e., thrombosis in the main trunk of the portal vein, with or without blood flow) on baseline imaging.
* Active or previously documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[except for diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). Patients without active disease in the last 5 years are excluded unless discussed with the Treating Physician and considered appropriate for EAP participation. The following are exceptions to this criterion:
* Patients with vitiligo or alopecia
* Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
* Any chronic skin condition that does not require systemic therapy
* Patients with celiac disease controlled by diet alone
* Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). HBV positive (presence of HbsAg and/or anti-HBcAb with detectable HBV DNA); HCV positive (presence of anti-HCV antibodies); HDV positive (presence of anti-HDV antibodies).
o Note: Testing required for subjects with a known history otherwise not required.
* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
* History of active primary immunodeficiency.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of EAP treatment. The following are exceptions to this criterion:
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
* Steroids as pre-medication for hypersensitivity reactions (e.g., CT scan pre-medication)
* Receipt of live attenuated vaccine within 30 days before first dose of treatment. Note: patients, if enrolled, should not receive live vaccine while receiving study treatment, and up to 30 days after the last dose of study treatment.
* Previous randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
* Patients who have received anti-PD-1, anti-PD-L1, or anti-CTLA-4 before the first dose of EAP treatment.
Pulsed Electric Field Ablation for Metastatic Breast Cancer
This phase I trial evaluates image-guided pulsed electric field ablation using the Aliya Pulsed Electric Field System to destroy superficial soft tissue lesions in adults with metastatic breast cancer.
NCT07487844 · Phase N/A · University of California, San Francisco
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
1. Participants must have histologically or cytologically confirmed metastatic breast cancer.
2. Confirmed documented soft tissue involvement via imaging or biopsy, with at least one measurable lesion with a cutaneous and/or subcutaneous component that is at least 1 cm in size but no greater than 5 cm in size and that can be safely accessed under image guidance. Up to 3 lesions that meet these criteria may be treated with PEF ablation therapy.
3. There are no limits on the amount of prior or concurrent anti-cancer therapies, but patients must be medically able (in the opinion of referring provider and treating investigator) to withhold their systemic therapy for breast cancer one week before the PEF ablation and for 2 weeks after the procedure.
4. Age ≥18 years
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Adequate Bone Marrow Function:
1. Absolute neutrophil count ≥1,500/microliter (mcL).
2. Platelets ≥100,000/mcL.
7. Not on or able to withhold anticoagulation or antiplatelet therapy per Society of Interventional Radiology periprocedural guideline.
8. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months (as documented in the medical record) are eligible for this trial.
9. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (as documented in the medical record), if indicated.
10. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (as documented in the medical record).
11. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
12. The effects of pulsed electric field on the developing human fetus are unknown. For this reason individuals of reproductive potential must agree to use adequate contraception: (e.g., hormonal or barrier method of birth control; abstinence, etc.) for the duration of study participation and for 4 weeks after last administration of study treatment. Should a study participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately.
Exclusion Criteria:
1. Has not recovered from adverse events due to prior/concurrent systemic anti-cancer therapy to ≤ Grade 2 (CTCAE v5.0) or baseline (other than alopecia).
2. Individuals with pacemakers or other electronic implant devices.
3. Individuals who are unable or unwilling, or with medical contraindication, to undergo moderate sedation and local anesthesia.
4. Pregnant individuals are excluded from this study because there is unknown risk of PEF on fetus.
5. Breastfeeding/chestfeeding individuals are excluded from this study because there is unknown risk on nursing infants; breastfeeding/chestfeeding should be discontinued prior to initiating study treatment.
6. Individuals with any condition or social circumstance that, in the opinion of the treating investigator, would impair the participant's ability to comply with study procedures.
Study of PSMA-targeted Therapy and Androgen Receptor Suppression in Low-volume Metastatic ProstatE Cancer: SPARKLE Trial
Phase II trial testing addition of the PSMA-targeted radioligand therapy 177Lu-PSMA-617 to leuprolide-based androgen deprivation (with or without abiraterone/prednisone) in patients with low-volume, hormone-sensitive metastatic (de novo or recurrent) prostate cancer.
NCT07650240 · Phase 2 · Mayo Clinic
Recruiting sites: Minnesota
Read full eligibility criteria
Inclusion Criteria:
* Male patients aged 18 years or older
* Signed informed consent must be obtained prior to participation in the study
* Histologically confirmed adenocarcinoma of the prostate
* Prior treatment with radical prostatectomy or radiation therapy for localized disease is required
* Prior treatment with ADT or androgen receptor pathway inhibitor (ARPI) or cytotoxic chemotherapy is permitted if:
* The last treatment \> 12 months from enrollment on the trial
* The duration of treatment is less than 3 months and no evidence of disease progression on treatment
* Disease detected on PSMA PET/CT scan \[PSMA-avid low volume metastasis (LVM)\]. Patients with standardized uptake value maximum (SUVMax) lesion/liver \>1 \[molecular imaging PSMA (miPSMA) score of 2\] or lesion/parotid \> 1 (miPSMA score of 3) would be included. PET scanners used in the study will comply with current guidelines established by the European Association of Nuclear Medicine (EANM) Research Limited (Ltd) (EARL) for harmonizing PET/CT image acquisition and reconstruction
* Patients with hormone sensitive low volume metastatic disease (LVM); either de novo metastatic or recurrent disease. LVM, as assessed on PSMA PET/CT is defined as:
* =\< 10 total metastatic spots
* Lymph nodes with short axis of =\< 2.5 cm
* Total tumor volume (TTV) \< 200 mL
* =\< 4 bone metastases
* No brain or liver metastases
* Eastern Cooperative Oncology Group (ECOG) performance 0 - 2
* Hemoglobin \>= 9 g/dL
* Platelet count \>= 100,000/mm\^3
* Absolute neutrophil count \>= 1,500/mm\^3
* Serum bilirubin =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 x ULN
* Serum creatinine =\< 1.5 x ULN or an estimated glomerular filtration rate (eGFR) \>= 50 mL/min/1.73m\^2
* Able to start therapy within 28 days of screening
* Expected life expectancy \> 6 months
Exclusion Criteria:
* PSMA-undetectable disease defined as rising prostate specific antigen (PSA) with absence of PSMA-positive lesions in PSMA PET/CT imaging
* PSMA-negative disease defined as lesions detected on imaging that are deemed concerning for active cancer metastasis with PSMA SUVmax less than liver and meeting specific size criteria: lymph nodes with short axis of \>= 2.5 cm, visceral lesions with a solid appearance (soft tissue density) \>= 1 cm, and bone metastases with a measurable soft tissue component \>= 1 cm
* Patient with in-field failure (disease recurrence in prostate bed after primary definitive prostatectomy or radiotherapy)
* Patient with spinal metastatic disease-causing cord compression
* Patient with prior disease progression on ADT \[castration resistance prostate cancer (CRPC)\]
* Prior treatment with ADT or cytotoxic chemotherapy or ARPI within less than 12 months from enrollment on the trial
* Prior treatment with ADT or ARPI or cytotoxic chemotherapy is permitted only if more than 3 months treatment duration and no evidence of disease progression on treatment
* Patients with severe \[Common Terminology Criteria for Adverse Events (CTCAE) grade \> 2\] xerostomia
* Patients with well documented history of myelosuppression or renal disease that might impair their participation in the trial per medical advice
* Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible
* Estimated life expectancy \< 6 months
* Concurrent serious medical co-morbidities as determined by study investigator and expected to impair participation in the study
* Subjects with female partners of reproductive potential are required to use effective, medically acceptable methods of birth control (e.g., spermicide in conjunction with a barrier such as a condom or sexual abstinence) while on this study, and for 14 weeks after the last dose of 177Lu-PSMA-617
A Pilot Study of Ultra-High Dose Rate (ConformalFLASH®), for Reirradiation of Carcinoma of the Head and Neck
ConformalFLASH ultra-high dose-rate pencil-beam scanning proton SBRT (8 GyRBE x 5 fractions) is being studied for reirradiation of surgically unresectable, previously irradiated head and neck carcinoma.
NCT07644585 · Phase N/A · IBA Proton Therapy, Inc.
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
1. Patients must sign an informed consent document that indicates they are aware of the investigational nature of the treatment in this protocol as well as the potential risks and benefits
2. Patients ≥ 18 years old
3. Patients ineligible for or decline upfront surgical resection
4. Histologically confirmed diagnosis of carcinoma of the head and neck
5. Prior receipt of at least 45 GyRBE radiotherapy to the head and neck
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or evidence of similar in the electronic medical record
7. Life expectancy of more than 12 weeks
8. Ability to understand and the willingness to provide written informed consent and to follow the study procedures
Exclusion Criteria:
1. Receipt of prior head and neck radiotherapy within the prior 6 months
2. Surgical resection of the current disease in the head and neck
3. More than 3 areas of disease requiring reirradiation
4. Disease focus exceeding 6.5 cm in greatest dimension
5. Presence of distant metastatic disease
6. Involvement of any of the following structures: skin, carotid artery, or mandible
7. Receipt of concurrent chemotherapy during radiotherapy
8. Uncontrolled intercurrent illness including medical and psychiatric, and social situations that would limit compliance with study requirements
9. Enrolled in any other investigational studies that involve administrations of another cancer therapeutic (such as surgery, chemotherapy, immunotherapy) during RT
10. Pregnant and/or breastfeeding
A Study To Assess the Safety, Tolerability, and Efficacy of Imzokitug in Combination With Pumitamig and Platinum-Doublet Chemotherapy (PDCT) Versus Pumitamig and PDCT as First-line Treatment for Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Imzokitug, an anti-CCR8 monoclonal antibody depleting tumor-infiltrating regulatory T-cells, is being tested in combination with pumitamig (a PD-L1/VEGF-A bispecific antibody) and platinum-doublet chemotherapy versus pumitamig plus chemotherapy as first-line treatment for locally advanced or metastatic non-small cell lung cancer.
NCT07680764 · Phase 2 · Bristol-Myers Squibb
Recruiting sites: District of Columbia, Georgia, Kentucky, Maryland, Mississippi, Nebraska, New York, Ohio, Texas, Wisconsin
Read full eligibility criteria
Inclusion Criteria
* Participants must have histologically confirmed diagnosis of stage IV non-small cell lung cancer (NSCLC) (squamous or non-squamous) or recurrent unresectable disease per the American joint committee on cancer (AJCC) Staging System 9th edition.
* Participants must have no prior systemic anti-cancer therapy given as primary therapy for advanced or metastatic disease.
* Tumor tissue (fresh or archival) obtained within 5 months of enrollment (signing of informed consent) for each participant must be submitted by the site.
* Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Exclusion Criteria
* Participants must not have any documented actionable genomic alterations (AGAs) for which first line approved targeted therapies are indicated.
* Participants must not have prior treatment with immuno-oncology therapies.
* Participants must not have untreated central nervous system (CNS) metastases.
* Other protocol-defined Inclusion/Exclusion criteria apply.
A Study of 2141-V11 in People With Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma
2141-V11, an intratumorally administered CD40 agonist monoclonal antibody, is being added to standard first-line anti-PD-1 (nivolumab) with or without fluoropyrimidine therapy in patients with advanced esophageal, gastric, or gastroesophageal junction adenocarcinoma.
NCT07818018 · Phase 1/2 · Memorial Sloan Kettering Cancer Center
Recruiting sites: New Jersey, New York
Read full eligibility criteria
Inclusion Criteria:
* Histologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma
* Locally advanced unresectable or metastaticdisease at diagnosis
* On first line systemic therapy including fluoropyrimidine + anti-PD-1 therapy for advanced GEA (e.g. FOLFOX + nivolumab) for a minimum of 3 months and no more than 9 months.
* Platinum chemotherapy included in first line regimen has been discontinued or will be discontinued ≥2 weeks prior to first planned dose of 2141-V11
* Patients in the safety lead-in cohort must be on 5-FU
* Primary esophageal, gastric, or gastroesophageal junction tumor intact and visible at time of enrollment (within 1 month of 2141-V11 treatment initiation) on endoscopy
* Evaluable disease at time of 2141-V11 treatment initiation as defined per RECIST v1.1
* Able to undergo endoscopy
* Age 18 years or older
* ECOG performance status 0 to 1 (See Appendix I for performance status criteria)
* Adequate organ function as defined by:
* Absolute neutrophil count ≥1000/mcL
* Platelets ≥90,000/mcL
* Hemoglobin ≥8 g/dL
* Serum creatinine ≤1.5X ULN
* Serum total bilirubin ≤1.5X ULN OR Direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5X ULN, except patients with Gilbert's disease (≤3X ULN)
* AST and ALT ≤3X ULN
* Albumin ≥3 mg/dL Abbreviations: ALT, alanine aminotransferase; AST, aminotransferase; ULN, upper limit of normal.
Exclusion Criteria:
* Mismatch repair deficient (dMMR) disease by IHC or microsatellite instability (MSI-H) by next-generation sequencing
* Known HER2-positive disease (IHC 3+ or IHC 2+ and amplification via fluorescence in situ hybridization)
* Prior radiation therapy to primary esophageal, gastric, or gastroesophageal junction tumor
* Anti-PD-1 therapy in ongoing regimen has been discontinued for any reason
* Disease progression on frontline therapy
* Patients with active autoimmune disease requiring ongoing systemic steroids or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment.
* Ongoing systemic steroids or receipt of systemic steroid therapy exceeding prednisone 10 mg/day or equivalent within 7 days before first dose, except physiologic replacement or short-course premedication (e.g. as antiemetics or CT scan contrast premedication), or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment. Use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
* Patients with active infection on parenteral antibiotics
* Patients with history of grade 3 or higher immune related adverse events to anti-PD-1 therapy may only be enrolled with the permission of the study PI.
* Prior treatment before ongoing regimen for any reason with PD-1, PD-L1, or CTLA-4 inhibitors
* Currently participating in a therapeutic study and receiving study therapy or has participated in a therapeutic study within 4 weeks of the first dose of treatment. Radiographic protocols including protocols with experimental tracers are not considered therapeutic studies and are exempt.
* Known active central nervous system metastases and/or leptomeningeal disease
* HIV, HBV, and HCV testing do not need to be performed as part of the study. For patients with known HIV, HBV, and/or HCV infection:
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Unwilling to give written, informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study
A Study of Lurbinectedin in Combination With Durvalumab for the Treatment of Participants With ES-SCLC
Lurbinectedin, a DNA minor-groove-binding alkylating agent, combined with durvalumab, a PD-L1-blocking monoclonal antibody, is being studied as maintenance therapy in extensive-stage small cell lung cancer patients who have not progressed after first-line induction chemoimmunotherapy.
NCT07459634 · Phase 2 · Jazz Pharmaceuticals
Recruiting sites: California, Florida, Georgia, Kentucky, South Carolina
Read full eligibility criteria
Inclusion Criteria:
1. Participant has histologically or cytologically confirmed ES-SCLC (per Veterans Administration Lung Study Group staging system).
2. Participant has received 4 cycles of definitive platinum-based chemotherapy with at least 3 cycles of durvalumab
3. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
4. Must have a life expectancy of ≥ 12 weeks as assessed by the treating physician.
5. Adequate hematologic and end-organ function for at least 7 days prior to dosing.
6. Has a body weight \> 30 kg.
7. Adequate contraceptive precautions.
Exclusion Criteria:
1. Clinically confirmed leptomeningeal carcinomatosis.
2. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
3. Significant cardiovascular disease within 3 months prior to enrollment
4. History of another primary malignancy
5. Presence or history of Central Nervous System (CNS) metastases
6. History of allogeneic organ transplantation.
7. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan.
8. Any concurrent chemotherapy, study intervention, biologic, or hormonal therapy for cancer treatment.
9. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
10. Pregnant or breastfeeding or intending to become pregnant during the study or within 6 months after the last dose of study intervention.
A Study to Evaluate the Efficacy of VVD-133214 in Combination With Pembrolizumab Compared With Pembrolizumab Alone in Participants With Advanced Cancer of the Colon or Rectum
VVD-133214, an oral small-molecule Werner (WRN) helicase inhibitor, is being studied in combination with pembrolizumab versus pembrolizumab alone as first-line treatment for advanced/metastatic MSI-H and/or dMMR colorectal adenocarcinoma.
NCT07811193 · Phase 2 · Vividion Therapeutics, Inc.
Recruiting sites: Arizona, Michigan, West Virginia
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1
* Have a known microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) tumor status confirmed per local standard of care (SoC), and have histologically or cytologically documented advanced (unresectable and/or metastatic) colorectal adenocarcinoma (CRC)
* No prior systemic treatment for metastatic disease and not amenable to curative resection
* Participants must have documented MSI and/or dMMR tumor status determined as part of the routine diagnostic workup in a certified laboratory
* Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to Sponsor/central laboratory for retrospective central testing including a copy of a redacted pathology report if available
* Presence of measurable disease according to RECIST v1.1
* Adequate hematologic and end-organ function, defined using laboratory results obtained within 14 days prior to first dose of study treatment
* Females of childbearing potential must have negative serum pregnancy test before starting study treatment
Exclusion Criteria:
* Prior systemic treatment for advanced CRC. Participants may have received prior adjuvant chemotherapy as long as disease progression occurred at least 12 months after the last dose of adjuvant treatment
* Prior treatment with adjuvant immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents, etc.)
* Known active or uncontrolled central nervous system (CNS) or brain metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous meningitis
* Patients with active or history of autoimmune disease or immune deficiency that has required treatment in past 2 years
* History of malignancy other than CRC, within 5 years prior to screening. Participants with Lynch syndrome are not excluded.
* Participants requiring treatment with systemic immunosuppressive medication (such as corticosteroids) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
* Participants with active hepatitis B, hepatitis C or HIV
* Participants with known Werner Syndrome (WRN)
* Prior treatment with any WRN helicase inhibitor
BL-M14D1 Plus Atezolizumab vs Standard of Care in First-Line Extensive-Stage Small Cell Lung Cancer (BrenDeLL-Lung01)
BL-M14D1 (mechanism not stated in registry) plus atezolizumab is being compared to standard platinum-based chemoimmunotherapy as first-line treatment for extensive-stage small cell lung cancer.
NCT07625644 · Phase 3 · SystImmune Inc.
Recruiting sites: Arkansas, California, Florida, New Jersey, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed first-line (1L), extensive-stage (ES) small cell lung cancer (SCLC)
* Must be eligible to receive a platinum-based chemotherapy regimen in combination with an anti-PD-L1 inhibitor.
* At least one measurable lesion based on RECIST v1.1 per investigator assessment.
* An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
* Adequate organ function
Exclusion Criteria:
* Received any kind of platinum or etoposide treatment for limited stage (LS) SCLC within 6 months prior to enrollment.
* Participants who have received prior topoisomerase inhibitor-based ADC therapy.
* Participants with history of severe heart disease
* Participants with active autoimmune diseases and inflammatory diseases,
* Participants with other prior or concurrent malignancies except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years
* Other protocol-defined inclusion/exclusion criteria apply.
CREO - Microwave Ablation Feasibility Study
This trial evaluates the EUS-guided MicroBlate Fine microwave ablation device for local tumor ablation in patients with locally advanced, unresectable, or metastatic pancreatic or liver cancer.
NCT07817147 · Phase N/A · Banner Health
Recruiting sites: Arizona, California, Illinois, Minnesota, Tennessee, Texas, West Virginia
Read full eligibility criteria
Inclusion Criteria:
* Male or female ≥18 years of age
* Willing and able to provide written informed consent
* Histologically confirmed locally advanced, unresectable or metastatic cancer (Stage III or IV)
* At least 1 tumor that is indicated for MWA, and the location of target tumor must be accessible via EUS through the gastric wall (eg, pancreas, liver, etc).
* The tumor(s) must be ≥1 cm in diameter
Exclusion Criteria:
* Participant is a candidate for upfront resection of pancreatic cancer
* Participation in another clinical trial that involves local ablation or any other local therapy that could affect the target organ or lesions treated in this study
* Any condition that, in the opinion of the investigator, may increase the risk to the participant's safety or well-being
Defining the Ablative Dose for Y-90 TARE
This trial evaluates Yttrium-90 radiation segmentectomy using glass microspheres to define an optimal ablative radiation dose in patients with unresectable hepatocellular carcinoma, cholangiocarcinoma, or liver-dominant metastatic disease.
NCT07586046 · Phase 2 · Northwestern University
Recruiting sites: Illinois
Read full eligibility criteria
Inclusion Criteria:
* Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation.
* Age ≥18 years.
* Child-Pugh class A or B liver function
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Adequate organ and bone marrow function as defined below:
* Leukocytes (WBC) ≥ 3,000/mcL
* Absolute neutrophil count (ANC) ≥ 1,500/mcL
* Hemoglobin ≥ 9 g/dL
* Platelets ≥ 50,000/mcL
* Total bilirubin ≤ 3.0 mg/dL
* AST ≤ 100 U/L, ALT ≤ 120 U/L
* Creatinine ≤ 2.0 mg/dL or estimated GFR ≥ 40 mL/min/1.73 m²
* Ability to undergo imaging and laboratory evaluations required by the study.
* Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
* Extrahepatic metastases.
* Pregnant or breastfeeding individuals.
* Tumors requiring treatment of more than two Couinaud segments.
* Known hypersensitivity to gadolinium-based contrast agents.
* Contraindications to MRI (e.g., incompatible pacemakers, claustrophobia unresponsive to sedation).
* Coagulopathy or clinical instability precluding angiographic intervention.
* Prisoners or individuals under legal custody.
* Adults unable to consent.
* Individuals under 18 years of age.
Effects of Infusion Timing on Treatment Response in Solid Tumors
This trial randomizes patients with metastatic NSCLC or resectable HNSCC receiving standard PD-1/PD-L1 checkpoint inhibitor immunotherapy to morning versus afternoon infusion timing to assess effects on treatment response.
NCT07630168 · Phase 2 · UNC Lineberger Comprehensive Cancer Center
Recruiting sites: North Carolina
Read full eligibility criteria
Inclusion Criteria:
Cohort 1A and 1B:
* Participants with metastatic non-small cell lung cancer (NSCLC).
* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
* Subject is willing and able to comply with study procedures based on the judgement of the investigator.
* Age ≥ 18 years at the time of consent.
Cohort 2A and 2B:
* Participants with resectable head and neck squamous cell carcinoma (HNSCC)
* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
* Subject is willing and able to comply with study procedures based on the judgement
* of the investigator.
* Age ≥ 18 years at the time of consent.
Exclusion Criteria: For All Cohorts (1A,1B, 2A, 2B)
* Subject is currently using steroids (prednisone ≥10 mg or its equivalent) and that cannot be discontinued at least 7 days before starting standard of care treatment.
* Prior immune checkpoint inhibitors (ICI) such as programmed cell death protein 1(PD-1) or programmed death-ligand 1 (PD-L1) inhibitor or Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) treatment received less than 6 months from the time of screening.
* Subject is participating in another treatment clinical trial.
Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer
This trial tests quemliclustat, a CD73 inhibitor, added to enfortumab vedotin (a nectin-4-directed antibody-drug conjugate) and pembrolizumab (a PD-1 inhibitor) as first-line treatment for previously untreated unresectable locally advanced or metastatic urothelial carcinoma of the bladder, renal pelvis, or ureter.
NCT07667335 · Phase 1/2 · Fred Hutchinson Cancer Center
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Participants must be at least 18 years of age on the day of signing informed consent. Participant provides written informed consent for trial
* Participants must have previously untreated locally advanced or metastatic bladder cancer including bladder cancer \[stage IIIB: T1-T4N2-3M0, stage IVa: T4bAnyNM0 or AnyTAnyNM1a, and stage IVB: AnyTAnyNM1b clinical stage per American Joint Commission on Cancer (AJCC)\] or renal pelvis or ureter cancer \[stage IV: T4Nx-0M0, AnyTN1-2M0, AnyTAnyNM1 clinical stage per AJCC\]. Lymph node with ≥ 15 mm short axis or biopsy-positive for carcinoma will be considered pathologically enlarged and measurable
* Participants must have either conventional urothelial carcinoma or urothelial carcinoma variants. A review of pathology by a local expert genitourinary (GU) pathologist is required to confirm the diagnosis. Any component (%) of non-conventional urothelial noted on tumor specimen is allowed for only histologic subtypes listed below in up to 20% of participants enrolled in this study.
* Urothelial carcinoma with squamous differentiation
* Urothelial carcinoma with glandular differentiation
* Urothelial carcinoma with trophoblastic differentiation
* Nested urothelial carcinoma
* Tubular and microcystic urothelial carcinoma
* Micropapillary urothelial carcinoma
* Lymphoepithelioma-like urothelial carcinoma
* Plasmacytoid urothelial carcinoma
* Sarcomatoid urothelial carcinoma
* Giant cell urothelial carcinoma
* Lipid-rich urothelial carcinoma
* Clear cell (glycogen rich) urothelial carcinoma
* Poorly differentiated urothelial carcinoma
* Squamous cell neoplasms including pure squamous cell carcinomas, verrucous carcinomas and squamous cell papilloma
* Measurable disease by RECIST v 1.1
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
* Available baseline fresh biopsy tissue sample obtained in the protocol RG1712006 or RG1125031 though clinically indicated procedures or participants must be willing to undergo a baseline research biopsy when safe and feasible
* Participant must have an estimated life expectancy of at least 3 months
* Hemoglobin ≥ 9 g/dl
* Absolute neutrophil count: ≥ 1500/ µL
* White blood cell count: ≥ 3000/µL
* Absolute lymphocyte count: ≥ 1000/µL
* Platelet count: ≥ 100.000/µL (without transfusion support)
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2.5 x upper limit of normal (ULN)
* Total bilirubin: ≤ 1.5 mg/dl except for patients with Gilbert's syndrome who must have a total bilirubin ≤ 3 mg/dl
* Creatinine clearance: ≥ 30 ml/min/1.73m\^2 by the method of Chronic Kidney Disease Epidemiology Collaboration (CKI-EPI) or ≥ 30 ml/min by the method of 24 hour (h) clearance of creatinine calculation
* International Normalized Ratio (INR): \< 1.5
Exclusion Criteria:
* Participants who are receiving any other investigational agents or concurrent anticancer treatment. Participants must have adequate treatment washout period before treatment, defined as: Major surgery (≥ 4 weeks), palliative radiation therapy (≥ 1 weeks from completion of treatment if they have recovered from the acute toxic effect of radiotherapy), prior adjuvant immunotherapy (≥ 4 weeks)
* Participants whose tumors have any % neuroendocrine or small cell histology, glandular neoplasms, urachal carcinomas, tumor of mullerian type, mesenchymal tumors or urothelial tract hematopoietic and lymphoid tumors
* Participants considered to be medically unfit for EV-P regimen as per Investigator discretion
* Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use
* Participants who have experienced disease progression following neoadjuvant or adjuvant systemic therapy within 12 months prior to enrollment will not be eligible
* Patients with Fridericia's corrected QT interval (QTcF) interval at screening of \> 480 milliseconds.
* Note: For any QTcF \> 480 milliseconds on initial electrocardiogram (ECG), a follow-up ECG will be performed to confirm QTcF interval prolongation and exclude the patient from this study
* Participants with active systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma, inflammatory bowel disease). Participants with autoimmune endocrine disorders controlled by medical management (e.g. thyroid disorders, type 1 diabetes, or adrenal insufficiency) will not be excluded
* Participants who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count \< 350 cells/microliter
* Participants with known active hepatitis (i.e. Hepatitis B or C). Prior hepatitis (Hep) C infection is allowed as long as polymerase chain reaction (PCR) test is negative
* Participants with clinically inactive brain metastases may be included. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment
* Participants with new or progressive brain metastases (less or equal of 1 cm of larger diameter) are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the participant and the investigator favors participation in the clinical trial. Patients with leptomeningeal disease will be excluded
* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy of assessment of the investigational regimen are eligible for this trial
* Woman of childbearing potential with positive serum pregnancy test within 72 hours prior to enrollment. Active lactation is an exclusion criterion
Phase 1 Trial to Study JANX013 and JANX007 Combination in mCRPC
JANX007, a PSMA x CD3 protease-activated masked T-cell engager, is studied in combination with JANX013 (mechanism not stated in registry) in metastatic castration-resistant prostate cancer.
NCT07813637 · Phase 1 · Janux Therapeutics
Recruiting sites: Tennessee
Read full eligibility criteria
Key Inclusion Criteria:
* Male participants ≥ 18 years of age at the time of signing informed consent
* Histologically or cytologically confirmed adenocarcinoma of the prostate
For Dose Escalation:
\- Have received at least 1 novel ARPI (e.g., abiraterone acetate, enzalutamide, apalutamide, or darolutamide) in any setting and have received at least 1 taxane regimen (in any setting), or who are medically unsuitable or have actively refused treatment with a taxane regimen.
For Dose Expansion:
* Must be in the first-line or second-line setting for mCRPC or metastatic androgen pathway modulation resistant disease and must have received 1 novel ARPI in any setting.
* Adequate organ function
Key Exclusion Criteria:
* Prior treatment with any chimeric antigen receptor (CAR) T-cell therapy, any approved or investigational TCE, or any T-cell costimulatory agent
* Clinically significant cardiovascular disease
* Prior solid organ transplant
Sacituzumab Tirumotecan +/- Pembrolizumab in I/O Exposed Metastatic or Recurrent Ovarian Clear Cell Cancer
Sacituzumab tirumotecan, a TROP2-targeted antibody-drug conjugate, is studied alone or with pembrolizumab (anti-PD-1) in relapsed/metastatic ovarian clear cell carcinoma previously treated with platinum/taxane chemotherapy and an immune checkpoint inhibitor.
NCT07718854 · Phase 2 · Tufts Medical Center
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria
An individual is eligible for inclusion in the study if the individual meets all of the following criteria:
Type of Participant and Disease Characteristics
1. Age ≥18 years (at the time of informed consent).
2. Has a histologically-confirmed diagnosis of pure OCCC. Patients with mixed histologies that include a clear cell component will not be eligible for this trial.
3. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/ radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
4. Patients must have received at least one prior platinum and taxane-based chemotherapy regimen; maintenance treatment will not be counted as a separate regimen. Radiation therapy (including the use of chemotherapy as a radiosensitizer) will not count as a prior systemic regimen. There is otherwise no line limit for entry in to this trial.
5. Patients must have also received one prior line containing an immune checkpoint inhibitor (ICI). More than one prior line of ICI treatment will be exclusionary.
6. Participants with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
7. ECOG performance status 0-1
8. Is an individual of assigned female sex at birth
9. Participant is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a Person of Child-Bearing Potential (POCBP) OR
• Is a POCBP and:
\- Agrees to use of a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) beginning at the time of informed consent, during the study treatment, and for at least 210 days after the last dose of study drug. During this period, the participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction.
\- The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
\- Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5.
\- Abstains from breastfeeding during the study intervention period and for at least 10 days after study intervention.
\- Medical history, menstrual history, and recent sexual activity have been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
Informed Consent
10. The participant provides written informed consent for the study. Additional Categories
11. Has provided an archival tumor tissue sample (slides or block) for pathologic confirmation of diagnosis at Tufts Medical Center.
12. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible.
13. Adequate organ function as defined in protocol Table 3. Specimens must be collected within 10 days before the start of study intervention.
14. Any other medical condition that will prevent the safe administration of study drugs in the opinion of the treating physician.
15. Be willing and able to comply with study procedures, laboratory tests, and other requirements of the study.
16. HIV-infected participants must have well-controlled HIV on ART, defined as:
a. Having a CD4+ T-cell count ≥350 cells/mm3 at the time of screening b. Having achieved and maintained virologic suppression, defined as confirmed HIV RNA level below 50 or the LLOQ using the locally available assay, at the time of screening and for at least 12 weeks before screening.
c. Absence of any AIDS-defining opportunistic infections within the past 12 months d. Being on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before randomization and agreeing to continue ART throughout the study Note: The ART regimen must not contain any antiretroviral medications that are strong CYP3A4 inducers/inhibitors/substrates. Refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor/substrate of CYP3A4.
HIV testing at screening is not otherwise required.
17. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization.
Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B testing at screening is not required unless:
* There is a known history of HBV infection
* Mandated by local guidelines
18. Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
Note: Participants must have completed curative antiviral therapy at least 4 weeks before randomization.
Hepatitis C testing at screening is not required unless:
* There is a known history of HCV infection
* Mandated by local guidelines
Exclusion Criteria
An individual must be excluded from the study if the individual meets any of the following criteria:
Medical Conditions 18. Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
19\. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention.
20\. Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
21\. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) 22. History of stem cell/solid organ transplant. Prior/Concomitant Therapy 23. Received prior treatment with a TROP2-targeted ADC. 24. Received prior treatment with a topoisomerase 1 inhibitor-containing ADC. 25. Received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention.
26\. Received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has radiation pneumonitis.
Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
27\. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
28\. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks.
Prior/Concurrent Clinical Study Experience 29. Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
30\. Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
Diagnostic Assessments 31. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of any organ (excluding carcinoma in situ of the bladder) who have undergone potentially curative resection are not excluded.
Note: Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
32\. Has CNS metastases and/or carcinomatous meningitis. 33. Has an active infection requiring systemic therapy. 34. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual's ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.
Other Exclusions 35. Severe hypersensitivity (Grades ≥3) to study interventions, any of their excipients, and/or to another biologic therapy.
36\. Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary.
Note: Participants who underwent major surgery must have adequately recovered from toxicity and/or complications from the surgery before starting study intervention.
37\. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
38\. History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Safety and Efficacy of PIPAC Using Single Agent Mitomycin in Solid Tumors
This phase 1 trial tests pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivering the DNA-crosslinking antibiotic mitomycin C directly into the peritoneal cavity in patients with unresectable peritoneal carcinomatosis from colorectal, small bowel, or high-grade appendiceal cancers who have completed first-line systemic therapy.
NCT07487168 · Phase 1 · H. Lee Moffitt Cancer Center and Research Institute
Recruiting sites: Florida
Read full eligibility criteria
Inclusion Criteria:
* Participants must have histologically confirmed peritoneal disease from colorectal, small bowel, or high grade appendiceal adenocarcinoma. High grade appendiceal cancers include moderate or poorly differentiated mucinous or non-mucinous adenocarcinoma, signet ring cell adenocarcinoma, or goblet cell adenocarcinoma. This can be established by image guided biopsy, diagnostic laparoscopy, or previous surgery.
* Patients must be ineligible for CRS/HIPEC through one of the following criteria: a) PCI score ≥16. b) Inability to achieve complete cytoreduction due to extent of disease. c) Significant small bowel involvement precluding a complete CRS. d) Unresectable disease in porta hepatis, pelvic side wall or other critical structure. e) Patients who decline invasive cytoreduction.
* Participants must be 18 years of age or older.
* Participants must have completed at least 4 months of first-line systemic therapy (5-FU based approach with or without biologic therapy).
* Participants must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
* Participants must have adequate organ and marrow function as defined below: a) absolute neutrophil count ≥1500/mcL. b) platelets ≥100,000/mcL. c) total bilirubin ≤ institutional upper limit of normal (ULN). d) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN. e) creatinine ≤ 1.5 institutional ULN. or f) glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2.
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should undergo a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification (see Appendix C).
To be eligible for this trial, participants should be class 2B or better.
* MMC is a known teratogen, for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration. For women of child-bearing potential a negative urine pregnancy test is required on the morning of surgery.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Participants who have received targeted therapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks for VEGF inhibitors, nitrosoureas or mitomycin C) prior to entering the study.
* Participants who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1), except for alopecia and chemotherapy induced peripheral neuropathy \< 2.
* Patients with extensive metastatic liver disease (\>50% liver volume) are excluded from the trial as are patients with brain metastases. Patients with non-peritoneal metastatic disease are otherwise eligible provided they meet the survival expectations of \>6 months.
* Patients with brain metastases are excluded
* Patients with bowel obstruction or need for nutritional support (i.e., TPN or tube feeds).
* Participants who are receiving any other investigational agents or enrolled on other research protocols that may interfere with compliance with requirements of the study.
* History of allergic reactions or poor tolerance attributed to compounds of similar chemical or biologic composition to MMC, fluoropyrimidines, or anesthesia medications.
* Participants with uncontrolled intercurrent illnesses.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because MMC is an antibiotic alkylating antineoplastic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MMC, breastfeeding should be discontinued if the mother is treated with MMC.
* Inability to safely perform laparoscopy due to previously noted adhesions or extensive prior surgery which the treating surgeon feels would exclude safe abdominal access.
* Life expectancy less than 6 months.
* Patients with history of thromboembolic complications that cannot discontinue for the perioperative duration.
Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma
Darovasertib, an oral PKC inhibitor, combined with crizotinib, an oral ALK/c-Met inhibitor, is being studied as adjuvant therapy in patients with high-risk non-metastatic uveal melanoma after primary local treatment.
NCT07804186 · Phase 3 · IDEAYA Biosciences
Recruiting sites: Arizona, California, Massachusetts, Michigan, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Primary Uveal Melanoma, classified as high-risk of relapse (AJCC Stage II or Stage 3)
* Completed primary local therapy (enucleation, proton beam therapy, plaque brachytherapy)
* ECOG performance status of 0 or 1
* Adequate organ function
* Age 18 or older
* Written informed consent and ability to comply
* Primary local therapy completed within 120 days before C1D1/randomization.
* Contraception requirements
Exclusion Criteria:
* Previous systemic treatment for Uveal Melanoma
* Clinical or radiological evidence of metastatic UM
* Concurrent malignant disease with the following exceptions: malignancies that were treated curatively and have not recurred within 2 years prior to randomization, completely resected basal cell and squamous cell skin cancers, any malignancy considered to be indolent and never required systemic therapy, and any type of carcinoma in situ receiving curative therapy (resection)
* Known AIDS related illness
* History of interstitial lung disease, active pneumonitis, or history of noninfectious pneumonitis requiring steroids
* History of syncope may be exclusionary, but will be reviewed on a case-by-case basis
* Active Hepatitis B or C infection
* Any gastrointestinal condition (eg, inflammatory bowel disease, major gastric or intestinal surgery) that could affect absorption or ability to swallow
* Females who are pregnant or breastfeeding
* Impaired cardiac function
* History of stroke within the last 6 months of randomization
* Ongoing use of medication use for infections, other antineoplastic therapies, or other prohibited medications, including medications that interact with the metabolism of darovasertib+crizotinib
* allergy to mammalian meat products or gelatin
Testing the Combination of Anti-Cancer Drugs, Botensilimab (AGEN1181) and Balstilimab (AGEN2034), After Standard Treatment for Colorectal Cancer, Combat Trial
Botensilimab (an anti-CTLA-4 monoclonal antibody) plus balstilimab (an anti-PD-1 monoclonal antibody) are being tested as post-adjuvant immunotherapy to clear minimal residual disease in patients with ctDNA-positive, resected stage II/III colorectal adenocarcinoma.
NCT07551596 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: Louisiana, Texas
Read full eligibility criteria
Inclusion Criteria:
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab (AGEN1181) in combination with balstilimab (AGEN2034) in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (or Karnofsky ≥ 60%)
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
* Patients with documented Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* Creatinine clearance ≥ 40 mL/min
* Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation
* Histological confirmation of colorectal cancer (adenocarcinoma) (CRC)
* Post-R0 resection of stages II and III CRC and all planned adjuvant therapies have been completed. Patients with rectal cancer who have completed total neoadjuvant therapy and have complete clinical response (cCR) and are on wait-and-watch approach will be permitted as long as they have no radiographic and endoscopic evidence of disease recurrence at the time of enrollment
* No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay
* Evident MRD as defined by positive ctDNA (Signatera™ MRD) assay. MRD status will be confirmed with the Signatera™ assay prior to initiation of study therapy. MRD positivity is defined based on testing performed after completion of planned standard treatment (e.g., surgery or chemotherapy), provided assessments occur at least 3 weeks post-surgery (if no adjuvant therapy is planned) and at least 3 weeks after last chemotherapy (if adjuvant therapy is given) to avoid transient false positives. The window from MRD positivity to first dose should be no more than 90 days
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* The effects of botensilimab (AGEN1181) and balstilimab (AGEN2034) on the developing human fetus are unknown. Women of child-bearing potential \[refer to MD Anderson (MDA) Policy CLN 1114\] must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 4 months after the last dose. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months)
* History of hysterectomy or bilateral salpingo-oophorectomy
* Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy)
* History of bilateral tubal ligation or another surgical sterilization procedure.)
* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of administration. In addition, women of childbearing age should not donate egg(s) and men should not donate sperm for the duration of study participation and 6 months after completion of the last dose of botensilimab (AGEN1181) and balstilimab (AGEN2034).
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab (AGEN1181) and balstilimab (AGEN2034)
* Patients that are pregnant, breast feeding, or planning to become pregnant while enrolled in the study, up to the end of treatment (EOT) visit, are excluded from this study because botensilimab (AGEN1181) and balstilimab (AGEN2034) are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab (AGEN1181) and balstilimab (AGEN2034), breastfeeding should be discontinued if the mother is treated with botensilimab (AGEN1181) and balstilimab (AGEN2034)
* Patients with microsatellite instability (MSI-high) or deficient mismatch repair (dMMR) CRC (MMR/MSI testing is required prior to enrollment)
* Concurrent treatment with a drug with which the interactions are considered clinically significant by the investigator. Major surgical procedure or significant traumatic injury within 21 days before start of study medication \* Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment
* Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for metastatic (m)CRC
* Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant)
* Patients with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Patients with known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Patients with corrected QT interval (QTc) \> 470 ms on electrocardiogram (EKG) at screening
* Patients with clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial. Stable, well-controlled conditions such as vitiligo, type 1 diabetes, or hypothyroidism on replacement can be allowed
* Failure to recover from any toxicity related to previous anticancer treatment to ≤ grade 1 for toxicities that may overlap with botensilimab (AGEN1181) and balstilimab (AGEN2034) (e.g., diarrhea, cutaneous toxicity) and to ≤ grade 2 for all other toxicities
* Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted)
* Evidence of any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug
* Patients with a history of (non-infectious) pneumonitis that required steroids, ongoing pneumonitis, or history of interstitial lung disease
* Patients with grade \>= 3 proteinuria (\> 3.5 g/24 hours)
* Patients with grade \>= 3 hypertension (systolic blood pressure \> 160 or diastolic blood pressure \> 100)
* Active autoimmune disease requiring systemic treatment in the past 2 years (e.g., steroids \> 10 mg prednisone equivalent, biologics, other immunosuppressants)
* Active or prior inflammatory bowel disease (Crohn's, ulcerative colitis, microscopic colitis). This is especially critical in colon cancer patients where you might otherwise capture inflammatory bowel disease (IBD)-associated CRC
Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION)
Lorigerlimab, a bispecific antibody targeting PD-1 and CTLA-4, is being studied as induction immunotherapy in treatment-naive recurrent, metastatic, or persistent cervical cancer not amenable to curative surgery/radiation.
NCT05475171 · Phase 2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
Inclusion criteria will be assessed within 28 days of starting study treatment:
1. Ability to provide signed informed consent
2. Age ≥ 18 years at time of study entry
3. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
4. Biopsy or CT scan confirmed recurrent, metastatic, or persistent cervical cancer
5. One of the following histologic subtypes: squamous cell carcinoma, adenosquamous, or adenocarcinoma
6. Not amenable to curative treatment (e.g. surgery and/or radiation)
7. Eastern Cooperative Oncology Group performance status 0 - 1
8. Measurable disease by RECIST v1.1
9. Adequate normal organ and marrow function as defined below.
1. Hemoglobin ≥8.0 g/dL.
2. Absolute neutrophil count (ANC) \> 1000/mm3
.
3. Platelet count ≥100 x 109
/L (\>75,000/mm3
).
4. Serum bilirubin ≤1.5 x ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
5. AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, in which case it must be ≤5x ULN.
6. International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
7. Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
10. Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
1. Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiationinduced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
11. If vaccinated against COVID-19, the last vaccine dose must be 14 days or greater from the first investigational product administration.
12. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the PI
Exclusion Criteria:
Exclusion criteria will be assessed within 28 days of starting study treatment:
1. Prior systemic chemotherapy except when used with concurrent radiation therapy
2. Is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
3. Previous immune checkpoint inhibitor therapy or cytokines
4. Ongoing or active systemic infection, active hepatitis B or C infection, or known uncontrolled HIV, that might affect host immunity. Patients with stable, controlled HIV (defined as CD4+ T-cell counts ≥ 350 cells/uL, on established antiretroviral therapy for at least 4 weeks, and have an HIV viral load less than 400 copies/mL prior to enrollment) are eligible for trial inclusion.
5. History of chronic obstructive pulmonary disease or other intrinsic lung disease requiring systemic steroid therapy, oxygen, or hospitalization
6. History of clinically significant cardiovascular disease or QTcF \> 470 within 12 months from first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular event, or cardiac arrhythmia associated with hemodynamic instability. Note: medically controlled arrhythmia would be permitted.
7. History of immunodeficiency or receiving chronic systemic steroid or other immunosuppressive therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Steroid premedications for radiologic contrast allergy are permitted.
8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
9. Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
11. Other illnesses/conditions that in the investigator's opinion would adversely affect the safety of checkpoint inhibitor therapy.
A Study of ASP2138 Together With Chemotherapy and Pembrolizumab in Adults With Gastric Cancer
ASP2138, a CLDN18.2 x CD3 bispecific antibody, is being tested in combination with chemotherapy and pembrolizumab versus placebo plus chemotherapy (with or without pembrolizumab) for first-line HER2-negative, CLDN18.2-positive locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.
NCT07673887 · Phase 3 · Astellas Pharma Global Development, Inc.
Recruiting sites: Minnesota
Read full eligibility criteria
Inclusion Criteria:
* Participant has histologically or cytologically confirmed gastric or GEJ adenocarcinoma.
* Participant has radiographically confirmed, locally advanced unresectable or metastatic disease within 28 days prior to randomization.
* Participant has predicted life expectancy \>= 12 weeks.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a women of childbearing potential (WOCBP)
* WOCBP who has a negative serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum human chorionic gonadotropin (HCG) and a demonstrated nonpregnant status through additional testing are eligible.)
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period, and at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after the final administration of study intervention.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final administration of study intervention.
* Male participant must not donate sperm during the treatment period and for 6 months after the final administration of study intervention.
* Participant has radiologically evaluable disease (measurable and/or non measurable) according to RECIST V1.1, per investigator assessment, \<= 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy \<= 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
* Participant's tumor is HER2-negative (HER2 immunohistochemistry (IHC) score 0+/1+ or HER2 IHC score 2+/in situ hybridization (ISH) negative) as determined by local or central testing.
* Participant has provided an formalin-fixed paraffin-embedded (FFPE) tumor sample which meets the requirements of the study as specified in the laboratory manual.
* Participant has CLDN18.2-positive tumor as determined by central testing.
* Participant has a valid programmed death-ligand 1 (PD-L1) result as determined by central testing of a tumor sample.
* Participant with known microsatellite instability-high or mismatch repair deficient status may enroll as long as their tumor expresses PD-L1 combined positive score (CPS) \>= 1 as determined by central IHC testing.
* Participant has ECOG performance status 0 to 1.
* Participant must meet all of the criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In case of multiple central laboratory data within this period, the most recent data should be used (transfusion is allowed, but posttransfusion hemoglobin \[24 hours or later following transfusion\] must be \>= 9 g/dL).
South Korea Specific:
* Participant is \>= 19 years of age at the time of signing informed consent.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a WOCBP
* WOCBP who has a negative serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum HCG) and a demonstrated nonpregnant status through additional testing are eligible.)
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period, and at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for at least 15 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period, and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
* Male participant must not donate sperm during the treatment period and for 12 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
Japan Specific:
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a WOCBP
* WOCBP who has a negative serum pregnancy test at screening with a medical interview and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum HCG and a demonstrated nonpregnant status through additional testing are eligible.)
Exclusion Criteria:
* Participant has mixed histology or non-adenocarcinoma gastric or GEJ cancer.
* Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to randomization.
* Participant has gastrointestinal (GI) perforation, fistulae, untreated gastric ulcers that would preclude the participant from study participation, or any arterial thromboembolic event within 6 months, or any significant GI bleeding or any significant venous thromboembolism within 3 months prior to randomization.
* Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
* Participant has pre existing peripheral neuropathy \> Grade 1.
* Participant has poorly controlled hypertension.
* Participant has significant cardiovascular disease, including any of the following:
* Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization.
* corrected QT (QTc) interval \> 450 msec for male participants; QTc interval \> 470 msec for female participants.
* Documented history or family history of congenital long QT syndrome.
* Cardiac arrhythmias requiring anti-arrhythmic medications (Exception: Participant with rate-controlled atrial fibrillation for \> 1 month prior to randomization is eligible), obligate use of cardiac pacemaker, or a history of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes).
* Participant has a diagnosis of immunodeficiency or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Participants that require replacement therapy (e.g., thyroxine (T4), insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled.
* Participant has psychiatric illness or social situations that would preclude study compliance.
* Participant has history of another malignancy within 3 years prior to randomization, or any evidence of residual disease from a previously diagnosed malignancy. Participants with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
* Participant has history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease.
* Participant has known, existing uncontrolled coagulopathy. Concomitant treatment with medications that affect the coagulation cascade with an international normalized ratio (INR) \> 2 (e.g., vitamin K antagonists) is not allowed.
* Participant may receive low molecular weight heparin (LMWH) (such as enoxaparin and dalteparin) and direct oral anticoagulant (DOAC) for management of deep venous thrombosis (DVT).
* Participant has a history of bleeding diathesis or recent major bleeding events (i.e. Grade \>= 2 bleeding events 28 days prior to randomization).
* Participant has uncontrolled intercurrent illness.
* Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
* Participant is known to have human immunodeficiency virus (HIV) infection except for those with cluster of differentiation (CD) 4+ T cell counts \>= 350 cells/microliter (µL) and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months are eligible. NOTE: Screening for HIV infection should be conducted if indicated per local requirements.
* Participant is known to have active hepatitis B (positive hepatitis B surface antigen \[HBsAg\]) or hepatitis C infection. Testing is required for known history of these infections or as mandated by local requirements. NOTE: Screening for these infections should be conducted if indicated per local requirements.
* For participant who is negative for HBsAg, but hepatitis B core (HBc) antibody positive, an hepatitis B virus (HBV) DNA test will be performed and if positive the participant will be excluded.
* Participant with positive hepatitis C virus (HCV) serology, but negative HCV RNA test results is eligible.
* Participant treated for HCV with undetectable viral load results is eligible.
* Participant has a known history of a positive test for tuberculosis or known active tuberculosis infection. NOTE: Screening for these infections should be conducted per local requirements.
* Participant has known complete dihydropyrimidine dehydrogenase (DPD) deficiency (screening for DPD deficiency should be conducted per local requirements).
* Participant has pernicious anemia or other anemias due to vitamin B12 deficiency.
* Participant has received prior systemic chemotherapy and/or immunotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, a maximum of 1 cycle of mFOLFOX6 or CAPOX with or without immunotherapy (for those participants with CPS \>= 1) is allowed to be administered prior to randomization (Note: No dose modifications are allowed for the lead-in treatment). Participants may have received either neoadjuvant or adjuvant chemotherapy, immunotherapy, or other systemic anticancer therapies as long as they were completed at least 6 months prior to randomization and there was disease progression occurs at least 6 months after the last dose. Participant may have received treatment with herbal medications that have known antitumor activity \> 28 days prior to randomization. NOTE: Participants must have recovered from all AEs due to previous therapies to \<= Grade 1 or baseline.
* Participant has received systemic immunosuppressive therapy, including systemic corticosteroids \<= 7 days prior to randomization. Participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
* Participant has had a major surgical procedure \<= 28 days before randomization and has not fully recovered.
* Participant has received a CLDN18.2-targeted therapy \<= 28 days or 5 half-lives (whichever is longer) prior to randomization, or participant has experienced Grade \>= 3 GI toxicity after receiving a CLDN18.2-targeted therapy.
* Participant has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma \<= 14 days prior to randomization and has NOT recovered from any related toxicity. A 7-day washout is permitted for palliative radiation (\<= 14 days duration time for radiotherapy) to non-CNS disease.
* Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX-40, CD137) unless received in the perioperative setting.
* Participant received a live or live-attenuated vaccine within 30 days prior to randomization. NOTE: Inactivated seasonal influenza vaccines are allowed.
* Participant has received treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to randomization or within 5 half-lives of the drug, whichever is shorter.
* Participant has received any investigational therapy within 28 days prior to randomization or within 5 half-lives of the investigational medicinal product (IMP), whichever is longer.
* Participant has any condition including clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
* Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any study intervention.
EU Specific:
* Participant has known complete DPD deficiency (screening for DPD deficiency should be conducted per local requirements). All participants in the EU must be tested for DPD deficiency before receiving fluoropyrimidine-based chemotherapy, in accordance with European Society for Medical Oncology and European Medicines Agency (EMA) recommendations.
A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma
Ivonescimab, a PD-1/VEGF bispecific antibody, is being studied in combination with enfortumab vedotin versus pembrolizumab plus enfortumab vedotin as first-line treatment for previously untreated locally advanced or metastatic urothelial carcinoma.
NCT07815665 · Phase 2/3 · Summit Therapeutics
Recruiting sites: Arizona, California, District of Columbia, Florida, Minnesota, Tennessee, Washington
Read full eligibility criteria
Inclusion Criteria:
* 18 years and older
* ECOG 0-1
* Life expectancy ≥ 6 months
* Histologically documented unresectable LA/mUC (transitional cell carcinoma) of the bladder, renal pelvis, ureter, or urethra with ≥50% urothelial carcinoma component
* No prior systemic therapy for LA/mUC
* At least one measurable non-cerebral lesion according to RECIST v1.1
* Adequate organ function
Exclusion Criteria:
* Locally advanced disease that is resectable or suitable for local therapy with curative intent.
* Tumors containing any small cell or neuroendocrine differentiation
* Ongoing sensory or motor neuropathy Grade 2 or higher.
* Radiographic findings consistent with a high risk of bleeding
* History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction, extensive bowel resection within 6 months prior to first dose.
A Study to Compare the Steady-State Bioavailability of Injectable Letrozole SIE and Oral Letrozole in Post-Menopausal Women With Hormone Receptor Positive Early Breast Cancer
Injectable long-acting letrozole (Letrozole SIE), an aromatase inhibitor, is compared to standard oral letrozole for steady-state bioavailability in postmenopausal women continuing extended adjuvant endocrine therapy for HR-positive early breast cancer.
NCT07401381 · Phase 1 · Rovi Pharmaceuticals Laboratories
Recruiting sites: California, Florida
Read full eligibility criteria
Inclusion Criteria:
* Women with weight of ≥50 kg and a Body Mass Index (BMI) ≥19 kg/m2 and ≤39 kg/m2
* Postmenopausal women.
* Women with confirmed diagnosis of HR+/HER2- or HR+/HER2+ early stage breast cancer who have completed at least 5 years of endocrine therapy, at least 2 years of which were with letrozole. Participants at a low risk of relapse, as assessed by the investigator, can also be eligible after completing 4 years of adjuvant endocrine therapy, at least 2 of which were with letrozole.
* Women in good health.
* Women who have undergone breast imaging per applicable guidelines (e.g., mammogram) within the last 12 months with no evidence of malignancy (documentation required), and if not done, must be willing to have 1 performed prior to baseline.
Exclusion Criteria:
* Presence of an uncontrolled, unstable, clinically significant medical condition.
* Have used estrogen or progesterone systemic or topical therapy, oral contraceptives, androgens, LH-releasing hormone analogs, prolactin inhibitors, or antiandrogens within 3 months prior to screening.
* Use of inducers or inhibitors of CYP3A4 and CYP2A6.
* Diagnosed with osteoporosis.
* Preexisting cardiovascular disease
* Positive result for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or HIV antibodies.
A Study Evaluating Ficerafusp Alfa (BCA101) QW in Combination With Pembrolizumab vs Alternative Ficerafusp Alfa Dosing in 1L R or M HNSCC
Ficerafusp alfa, a bifunctional anti-EGFR/anti-TGF-beta monoclonal antibody, is being studied at alternative dosing regimens in combination with pembrolizumab as first-line treatment for PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma.
NCT07807163 · Phase 2 · Bicara Therapeutics
Recruiting sites: Florida, Louisiana, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Age ≥18 years on the day the Informed Consent Form is signed.
* Histologically or cytologically confirmed R or M HNSCC. Eligible primary tumor locations are oral cavity, hypopharynx, larynx or oropharynx (with documented HPV-negative disease if presenting with OPSCC). Note: primary tumor location of paranasal sinuses and nasopharynx, any histology are excluded.
* No prior systemic therapy administered in the R or M setting; and completed systemic therapy \>6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.
* Archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.
* PD-L1 CPS ≥1.
* Measurable disease based on RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function, as defined in the protocol.
Exclusion Criteria:
* Disease suitable for local therapy administered with curative intent.
* Prior treatment with anti-TGFβ therapy.
* Prior therapy with an anti-EGFR antibody (exception: radio sensitizing agents and multimodal treatment for locoregionally advanced disease).
* Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFR therapy or other murine proteins.
* Prior therapy with an immune checkpoint inhibitor completed within 6 months prior to study treatment initiation.
* Progressive disease \<6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.
* Life expectancy less than 3 months.
* Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded.
* Current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment.
* Subject participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy.
* Active autoimmune disease requiring systemic treatment in the past 2 years.
* Subjects with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment.
* Subjects with a known history of hepatitis C virus (HCV) who have not completed curative antiviral treatment or have an HCV viral load above the limit of quantification at Screening.
* Known history of human immunodeficiency virus (HIV).
* Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.
* Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer.
* Any condition requiring systemic treatment with either corticosteroids (\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days prior to the first dose of study treatment, except for topical, intranasal, intrabronchial, or ocular steroids.
* Use of a live or live attenuated vaccine within 4 weeks prior to Screening.
A Study of ASP388B Given by Itself and With Standard Therapies in Participants With Solid Tumors
ASP388B, an agent whose mechanism is not stated in the registry, is being studied alone or combined with pembrolizumab, carboplatin, oxaliplatin, or 5-fluorouracil in locally advanced or metastatic solid tumors including HNSCC, esophageal squamous cell carcinoma, castration-resistant prostate cancer, squamous NSCLC, and small cell lung cancer.
NCT07730021 · Phase 1/2 · Astellas Pharma Global Development, Inc.
Recruiting sites: New York, Virginia
Read full eligibility criteria
Inclusion Criteria:
For the ASP388B monotherapy dose escalation (excluding the tumor-specific backfill participants), the following criteria apply:
* Participant has a confirmed diagnosis of locally advanced unresectable or metastatic solid tumors.
* Participant has progressed on, is ineligible for, or has refused all available standard therapies (no limit to the number of prior treatment regimens).
* Prior exposure to B7-H3, STING agonist or TopI directed therapy is allowed.
* Participant must have one of the following malignancies (for all tumor types, any compounds of neuroendocrine histology is ineligible): HNSCC, ESCC, mCRPC, sqNSCLC, SCLC
* For mCRPC
* Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (including but not limited to abiraterone, enzalutamide and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen).
* Participants must have undergone bilateral orchiectomy or must be on continuous ADT with a GnRH agonist or antagonist.
* Total serum testosterone ≤ 50 ng/dL or 1.7 nmol/L
* Evidence of progressive disease, defined as ≥ 1 PCWG3 criteria: PSA level ≥ 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart; Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications; Appearance of ≥ 2 new lesions in bone scan
* Participants with mCRPC can be enrolled without measurable disease.
* For sqNSCLC
* Participants with known EGFR, ALK, ROS, BRAF or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed or discontinued treatment due to toxicity.
* For SCLC
* Metastatic or extensive stage (EC-SCLC)
For the ASP388B 2L+HNSCC monotherapy dose expansion (including the tumor-specific backfill participants from the monotherapy dose escalation), the following criteria apply:
* Participant has histologically or cytologically confirmed HNSCC.
* Tumors arising from the nasopharynx are excluded.
* Known PD-1/PD-L1 status and any HPV status is eligible.
* Participant has evidence of radiographic progression on or after the last regimen received.
* Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment.
* Participant has progressed, relapsed or discontinued treatment due to toxicity after local guidelines/SOC regimen for locally advanced or metastatic disease, and has received ≤ 3 prior lines of anticancer therapy in the locally advanced or metastatic setting.
* Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if relapsed or progressed ≤ 6 months after completion.
* No prior exposure to B7-H3, STING agonist or TopI directed therapy is allowed.
For the ASP388B 2L+ESCC monotherapy dose expansion (including the tumor-specific backfill participants from the monotherapy dose escalation), the following criteria apply:
* Participant has histologically or cytologically confirmed ESCC.
* Known PD-1/PD-L1 status and any HER2 status is eligible.
* Participant has evidence of radiographic progression on or after the last regimen received.
* Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment.
* Participant has progressed, relapsed or discontinued treatment due to toxicity after local guidelines/SOC regimen for locally advanced or metastatic disease, and has received ≤ 3 prior lines of anticancer therapy in the locally advanced or metastatic setting.
* Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if relapsed or progressed ≤ 6 months after completion.
* No prior exposure to B7-H3, STING agonist or TopI directed therapy is allowed.
For the ASP388B 1L HNSCC (Excluding NPC and Salivary Gland Tumors) combination therapy dose escalation and expansion (including the tumor-specific backfill participants from combination therapy dose escalation), the following criteria apply: (ASP388B + Pembrolizumab + Carboplatin + 5-FU):
* Participant has histologically or cytologically confirmed HNSCC excluding nasopharyngeal cancer (NPC) and salivary gland tumors.
* Known PD-1/PD-L1 status and any HPV status is eligible
* Participant has recurrent or metastatic disease that is incurable by local therapies.
* Participant has had no prior systemic therapy administered with the exception of systemic therapy completed \> 6 months prior if given as part of multimodal treatment with curative intent for nonmetastatic disease stages.
* No prior exposure to B7-H3, STING agonist or TopI directed therapy is allowed.
For the ASP388B 1L ESCC combination therapy dose escalation and expansion (including the tumor-specific backfill participants from combination therapy dose escalation), the following criteria apply: (ASP388B + Pembrolizumab + Oxaliplatin + 5-FU):
* Participant has histologically or cytologically confirmed ESCC.
* Known PD-1/PD-L1 status and any HER2 status is eligible
* Participant has had no prior systemic therapy administered with the exception of systemic therapy completed \> 6 months prior if given as part of multimodal treatment with curative intent for nonmetastatic disease stages.
* No prior exposure to B7-H3, STING agonist or TopI directed therapy is allowed.
For the ASP388B 1L ESCC combination therapy dose escalation and expansion
* Participant has a predicted life expectancy ≥ 12 weeks.
* Participant has at least 1 measurable lesion per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participant has an ECOG performance status of 0 or 1.
* Participant has adequate organ function as indicated by laboratory values (If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 14 days after any blood transfusion).
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of childbearing potential (WOCBP)
* WOCBP who has a negative urine or serum pregnancy test at screening with a medical interview and agrees to follow the contraceptive guidance from the time of informed consent through at least 7 months after final study intervention administration or after at least 9 months for participants with 1L ESCC receiving combination therapy, or per local labeling requirements, whichever is longer.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (approximately 7 months after final study intervention administration or after at least 9 months for participants with 1L ESCC receiving combination therapy, or per local labeling requirements, whichever is longer).
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 4 months after final study intervention administration or after at least 9 months for participants with 1L ESCC receiving combination therapy, or per local labeling requirements, whichever is longer.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 4 months after final study intervention administration or after at least 9 months for participants with 1L ESCC receiving combination therapy, or per local labeling requirements, whichever is longer.
Exclusion Criteria:
* Participant weighs \< 40 kg during screening.
* Participant has known active central nervous system (CNS) metastases. NOTE: A participant with CNS metastases who has been treated with surgery and/or radiation therapy, who is no longer taking pharmacologic doses of glucocorticoids and is neurologically stable, is eligible. Prophylactic use of anticonvulsants is permitted.
* Participant has any of the following:
* Any history of recurrent Grade 3 immune-related AEs (irAEs) or history of Grade 4 irAEs related to prior anticancer therapy.
* Participant has active or prior autoimmune or inflammatory disorders requiring systemic therapy within the past 2 years including inflammatory skin conditions, inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis or uveitis. The following are exceptions to this criterion:
* Participant with type 1 diabetes mellitus
* Participant with vitiligo or alopecia
* Participant with endocrinopathies stably maintained on appropriate replacement therapy
* Participant with any chronic skin condition that does not require systemic therapy
* Participant has leptomeningeal disease as a manifestation of the current malignancy.
* Participant has a known additional malignancy that requires active treatment, with the exception of any of the following:
* Adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
* Adequately treated stage I cancer from which the participant is currently in remission and has been in remission for ≥ 2 years
* Any other cancer from which the participant has been disease-free for ≥ 5 years
* Participant has a known history of HIV infection with AIDS-related complications. HIV testing will be conducted per local requirements.
* Participant has clinically significant cardiac disease, defined as any of the following:
* Clinically significant cardiac arrhythmias, including bradyarrhythmia and ventricular arrhythmia, which are poorly controlled; cardiomyopathy or moderate or severe valvular disease. NOTE: Rate-controlled atrial fibrillation is permitted.
* Congenital long QT syndrome.
* QTcF ≥ 470 msec at screening. ECGs will be performed in triplicate during screening; the average of the triplicate readings will be used in the calculation of QTcF. If the QTcF is prolonged in a participant with a pacemaker or a right-sided bundle branch block, the participant may be enrolled in the study if confirmed by the sponsor's medical monitor. Participant with a left-sided bundle branch block will be excluded.
* History of clinically significant cardiac disease or congestive heart failure greater than NYHA Class II or LVEF measurement of \< 50% at baseline. Participant must not have had acute coronary syndrome, new-onset angina or coronary revascularization (PCI/CABG) within the past 12 months.
* Uncontrolled hypertension, defined as systolic BP \> 160 mmHg or diastolic BP \> 100 mmHg that has been confirmed by 2 successive measurements, despite optimal medical management.
* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 3 months before start of study intervention.
* Presence of cardiac injury syndromes: recent cardiac surgery, pacemaker/implantable cardioverter defibrillator insertion, ablation within 3 months prior to screening, recent PCI, blunt or penetrating chest trauma
* Presence or history of pericarditis (acute, recurrent or restrictive), myocarditis or any pericardial effusion requiring drainage or other invasive procedures
* History of pericardial tamponade, pericardial involvement associated with connective tissue diseases, sarcoidosis, vasculitis; congenital absence of defect of pericardium; aortic dissection with blood tracking into the pericardial space (hemopericardium/tamponade); iatrogenic hemopericardium (e.g., catheter perforation)
* Significantly elevated cardiac biomarkers (troponins and NT-proBNP) that require cardiology referral at screening
* Participant has a history of pleurodesis with impaired lung mechanics, recent (\< 6 weeks) pleurodesis or pleural surgery (decortication, pleurectomy), drug-induced fibrosing ILD, trapped lung, complicated pleural effusion, uncontrolled malignant pleural effusion, idiopathic pulmonary fibrosis, pneumonectomy, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, noninfectious ILD/pneumonitis, fibrotic lung disease or connective tissue disorder with pulmonary involvement. Any participant with a history of radiation pneumonitis that required treatment (e.g., steroid) will be excluded, regardless of resolution. NOTE: Participant with previously diagnosed Grade 1 radiation pneumonitis is allowed to be screened for the study. However, radiation pneumonitis must be confined to the previously irradiated area of the lung and be completely resolved.
* Participant has current Grade ≥ 1 ILD/pneumonitis, evidence of active pneumonitis on screening chest CT scan, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. NOTE: If participant requires intermittent use of bronchodilators, inhaled steroids or local steroid injections, they will not be excluded.
* Participant has pericardial disease related to prior radiation therapy.
* Participant has a confirmed SpO2 \< 92% at screening.
* Participant requires chronic oxygen supplementation therapy inclusive of noninvasive ventilation or bilevel positive airway pressure.
* Participant has any lung or heart disease (e.g., asthma, COPD, congestive heart failure) with uncontrolled symptoms or recent exacerbation or which may confound pulmonary safety assessments.
* Participant is at a significant risk of bleeding due to medical condition(s) or recent major bleeding (e.g., bleeding in critical site or requiring transfusions).
* Participant has current peripheral neuropathy Grade ≥ 2 (specific for platinum-containing cohorts only).
* Participant has a history of Grade ≥ 2 hearing loss (specific for platinum-containing cohorts only).
* Participant has received any strong inhibitors of CYP3A and CYP1A2 within 1 week or 5 half-lives (whichever is longer) or strong inducers of CYP3A within 2 weeks or 5 half-lives (whichever is longer) before the first dose of ASP388B.
* Participant has received prior B7-H3 targeting agents, STING agonists or TopI inhibitor (exception: monotherapy dose escalation cohorts).
* Participant has received prior radiation therapy within 2 weeks of the first dose of study intervention. Participant must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 3 weeks of radiotherapy) to non-CNS disease.
* Participant is receiving anticoagulants (vitamin K antagonists or direct oral anticoagulants) or antiplatelet agents. Low dose aspirin is allowed.
* Participant has received prior immuno-oncology anticancer therapy within 6 weeks prior to the first dose of study intervention. Participant has received any other prior anticancer therapy within 28 days or 5 half-lives, whichever is longer, of the first dose of study intervention.
ADCE-T02, a Tissue Factor Targeted Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours
ADCE-T02, a tissue factor-targeted antibody-drug conjugate carrying an exatecan topoisomerase I inhibitor payload, is being tested as monotherapy in a phase 1 trial for advanced solid tumors, with expansion cohorts in head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma.
NCT06597721 · Phase 1 · Adcendo ApS
Recruiting sites: Arkansas, Connecticut, Massachusetts, Missouri, New York, Texas
Read full eligibility criteria
Key Inclusion Criteria:
1. Patients must have pathologically confirmed unresectable advanced solid tumor
2. Patients who have undergone at least one systemic therapy and have progressive disease
3. Patients must have at least one measurable lesion as per RECIST version 1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Life expectancy ≥ 3 months.
6. Patients must have adequate organ function as indicated by laboratory values
7. Women of childbearing potential (WCBP), defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months must agree to use two effective contraceptive methods while on study treatment and for at least 7 months after the last dose of ADCE T02.
8. Male patients must agree to use condoms, even if they have had a successful vasectomy, while on study treatment and for at least 4 months after the last dose of ADCE T02.
Key Exclusion Criteria:
1. Prior treatment with any agent targeting Tissue Factor or any ADC with a topoisomerase 1 payload
2. Central nervous system (CNS) metastasis.
3. Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis, mucus pemphigoid or penetrating ocular transplants.
4. Persistent toxicities from previous systemic anti-neoplastic treatments
5. Known past or current coagulation defects leading to an increased risk of bleeding
6. Significant cardiac disease; recent myocardial infarction, acute coronary syndromes, congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias
7. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis
8. Prior second malignancy except for:
* Well treated basal cell carcinoma or squamous cell carcinoma of the skin.
* Low-risk prostate cancer with a Gleason score \< 7 and a PSA level \< 10 ng/mL
* Any cancer or in situ cancer the patient has been disease-free for ≥ 2 years.
Pacritinib in Participants With Metastatic Castrate-Resistant Prostate Cancer That Progressed on or After Prior Treatment With Androgen Receptor Signaling Inhibitors
Pacritinib, an oral JAK2/FLT3 inhibitor, is being studied in metastatic castration-resistant prostate cancer that progressed after prior androgen receptor signaling inhibitor therapy.
NCT07226713 · Phase 2 · Medical College of Wisconsin
Recruiting sites: Wisconsin
Read full eligibility criteria
Inclusion Criteria:
I. To be eligible for screening:
1. Patients aged ≥ 18 years.
2. Histologically or cytologically confirmed prostate adenocarcinoma.
3. Have current evidence of metastatic disease documented by either bone scan, CT/MRI and/or PSMA PET scan
4. Have disease that progressed while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) and during or after treatment with at least one androgen receptor signaling inhibitor (ARSI) (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide) for metastatic hormone-sensitive prostate cancer (HSPC) (mHSPC or nmHSPC) or mCRPC.
a. Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel. Disease progression could be prostate-specific antigen (PSA) based or radiographic progression per Prostate Cancer Working Group 3 (PCWG3) guidelines.
5. Screening serum testosterone \< 50 ng/dL.
6. Eastern Cooperative Oncology Group (ECOG), Performance Status grade 0-1 or Karnofsky Performance Status ≥ 70
7. No prior janus kinase2 (JAK2) inhibitor treatment.
8. Left ventricular cardiac ejection fraction of ≥ 50% by echocardiogram or multigated acquisition (MUGA) scan.
9. Adequate organ function as defined by the following laboratory values at screening:
1. Serum aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT), serum alanine transaminase (ALT) and serum glutamic pyruvic transaminase (SGPT) \< 2.5 x upper limit of normal (ULN).
2. Total serum bilirubin ≤ 1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 × ULN, the subject may be eligible).
3. Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
4. Estimated glomerular filtration rate (GFR) \> 45 ml/min using the Cockroft-Gault equation.
5. Platelets ≥ 100,000/mL independent of transfusion and/or growth factors within three months
6. Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within three months
7. Absolute neutrophil count ≥ 500/µL.
8. Serum albumin ≥ 3.0 g/dL.
9. Adequate coagulation defined by prothrombin time (PT)/international normalized ratio (INR) and PTT ≤ 1.5 ULN.
10. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
a. Practice effective barrier contraception and another effective method of birth control if he is having sex with a woman of childbearing potential during the entire study period and through 30 calendar days after the last dose of study agent
11. Ability to understand a written informed consent document, and the willingness to sign it.
II. To be eligible for treatment:
1. Patients must meet all screening criteria described above.
2. Patients must provide tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample. A tumor sample must be obtained within 30 days of treatment.
3. STAT5 activation levels need to be high, with positive STATA5 activation status defined as detectable nuclear localized Stat5 in \>5% of cancer cells from tissue obtained within 30 days of treatment.
Exclusion Criteria:
1. Patient does not have positive STAT5 activation status in PC core biopsies.
2. Previously treated with pacritinib.
3. Use of investigational agents within 28 days prior to randomization.
4. Use of other prohibited medications within seven days prior to Cycle 1, Day 1 or 5x half-life of the drug, whichever is longer.
5. Systemic treatment with a strong CYP3A4 inhibitor or inducer within 14 days prior to the start of treatment.
6. Uncontrolled hypertension.
7. Baseline severe hepatic impairment (Child-Pugh Class B \& C).
8. An intercurrent illness that is not controlled, such as active infection, psychiatric illness, or social situations that would limit compliance with study requirements.
9. Any chronic medical condition requiring a higher dose of corticosteroid than an equivalent of 10 mg prednisone/prednisolone per day.
10. Significant recent bleeding history, as defined as National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥ 2 within three months prior to start of treatment, unless precipitated by an inciting event (e.g., surgery, trauma, or injury).
11. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants (warfarin, direct oral anticoagulant, etc.), antiplatelet agents (except for aspirin dosages of ≤ 100 mg/day), anti-vascular endothelial growth factor (anti-VEGF) agents, and daily use of COX-1 inhibiting nonsteroidal anti-inflammatory agents (NSAIDs) within 14 days prior to the start of treatment.
12. Systemic treatment with medications that can prolong the QT interval within 14 days prior to the start of treatment. Shorter washout periods may be permitted with the approval of the PI, provided that the washout period is at least five half-lives of the drug prior to the start of treatment.
13. Any history of CTCAE v5.0 Grade ≥ 2 cardiac conditions within six months before treatment Day 1. Patients with asymptomatic Grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the principal investigator, if stable and unlikely to affect patient safety.
14. QT corrected for heart rate by Fridericia's cube root formula (QTcF) prolongation \> 450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia \[defined as serum potassium \< 3.0 mEq/L that is persistent and refractory to correction\]), or history of long QT interval syndrome.
15. New York Heart Association Class II, III, or IV congestive heart failure.
16. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication.
17. Active or uncontrolled inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation.
18. Other malignancy within three years prior to the start of treatment, other than curatively treated basal cell or squamous cell skin
19. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements.
20. Known seropositivity for human immunodeficiency virus.
21. Known active hepatitis A, B, or C virus infection.
Post-Marketing Study for Early-Stage Low-Risk Breast Cancer Treatment Using ProSense® Cryoablation (ChoICE Trial)
This post-marketing study evaluates the ProSense cryoablation device, a percutaneous freezing procedure, for local treatment of early-stage, low-risk breast cancer in patients aged 70+ receiving adjuvant endocrine therapy.
NCT07629206 · Phase N/A · IceCure Medical Ltd.
Recruiting sites: California, Oregon, Tennessee
Read full eligibility criteria
Inclusion Criteria:
1. Provision of a signed and dated informed consent form.
2. Age ≥70
3. Diagnosis of invasive ductal breast carcinoma (IDC) by core needle biopsy, meeting the following criteria:
* Unifocal primary disease
* Tumor size ≤1.5 cm in greatest diameter
* Estrogen receptor positive, Progesterone receptor positive, and HER2 negative
* Low-risk tumor biology, defined as Ki67\<15% or confirmed by genomic testing. In cases where Ki67 is ≥15%, low-risk status must be confirmed by genomic testing, which will prevail.
4. Lesions must be sonographically visible at the time of treatment
5. Clinically negative lymph node (N0).
Exclusion Criteria:
1. Presence of lobular carcinoma.
2. Presence of microinvasion or invasive breast carcinoma with extensive intraductal component (EIC), defined as DCIS component comprising ≥25%.
3. Evidence of lymphovascular invasion.
4. Presence of multifocal and/or multicentric breast cancer.
5. Presence of multifocal suspicious calcifications.
6. Presence of inflammatory features.
7. Previous ipsilateral breast radiation
8. Neoadjuvant endocrine treatment is provided to reduce the tumor size.
9. Prior or concurrent neoadjuvant chemotherapy, biological therapy, or other targeted neo-therapies.
10. Prior en bloc open surgical biopsy and/or lumpectomy for diagnosis/treatment of the index breast cancer.
11. Allergy to local anesthesia.
12. Any other reason defined as inoperable declared by a physician.
SKL35501 With SKL35502 Imaging in Adults With NTSR1 Positive Advanced Solid Tumors
SKL35501, an NTSR1-targeting small molecule radioconjugate delivering alpha-emitting 225Ac, is being studied as targeted radiotherapy in adults with relapsed/refractory advanced solid tumors (colorectal, pancreatic, biliary, gastric, esophageal, and head & neck squamous cell cancers) selected by NTSR1-positive SKL35502 SPECT imaging.
NCT07812805 · Phase 1 · SK Life Science, Inc.
Recruiting sites: Maryland, Pennsylvania
Read full eligibility criteria
Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply:
1. Signed ICF.
2. Participants should be ≥ 18 years (in the US) or ≥19 years (in South Korea) of age at the time of signing the ICF.
3. Histologically and/or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors (relapsed/refractory disease).
4. Selected advanced solid tumors (PDAC, CRC, BTC, HNSCC, EC, and GC) with sufficient target (NTSR1) expression confirmed by SKL35502 imaging as defined in Inclusion Criterion 5, that have progressed following at least one prior line of therapy or for which no other standard therapy with proven clinical benefit is currently available or recommended based on the Investigator's individual risk-benefit assessment. Patients with MSI-H/dMMR CRC must have previously received and progressed on, been intolerant to, or been deemed ineligible for an FDA-approved immune checkpoint inhibitor, unless such therapy is contraindicated.
5. Sufficient target (NTSR1) expression on SKL35502 imaging, defined as uptake above background in at least 1 RECIST v1.1 measurable lesion, with background activity defined in accordance with the Imaging Charter. For study eligibility, NTSR1 positivity will be determined locally at the site by the Investigator based on review by a qualified site nuclear medicine physician/radiologist, as applicable. SKL35502 images and required lesion documentation will also be submitted for central review for dosimetry, biodistribution, lesion alignment, image quality control, and consistency of image analyses across sites. Central review will not replace the site determination of eligibility except in equivocal cases requiring adjudication.
6. Patients with secondary metastasis to the CNS are eligible if they have had all brain metastases resected or have received radiation therapy ending at least 4 weeks prior to C1D1 and they meet all of the following criteria:
1. Residual neurological symptoms ≤ Grade 1
2. No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids (not exceeding a dose equivalent to prednisone 10 mg daily), provided the dose has been stable for at least 2 weeks prior to C1D1
3. Follow-up MRI or CT scan shows no progression of treated lesions and no new lesions.
7. Measurable disease on imaging, as assessed by RECIST v1.1 and/or RANO-BM for brain metastases (Eisenhauer et al, 2009).
8. ECOG performance status ≤ 2.
9. Minimum life expectancy ≥ 12 weeks at enrollment as determined by investigator
10. Willing to follow the contraception requirements as outlined:
1. For females:
WOCBP:
* Must have a negative serum pregnancy test performed within (≤) 14 days prior to dosing with SKL35502 (where demanded by local regulations; test may be required within 24 hrs. prior to dosing).
* Compliant with at least 2 highly effective contraceptive methods (e.g., oral contraceptives, IUD, condom with spermicide, etc.) throughout the study and for at least 8 months (i.e., corresponding to 5 half-lives + 6 months) following the last dose of SKL35501.
* Female patients must not be pregnant or lactating at study screening and during the course of the study and must not become pregnant for at least 8 months (i.e., corresponding to 5 half-lives + 6 months) following the last dose of SKL35501.
* Abstinence is not considered an adequate contraceptive method on its own.
* Women of non-childbearing potential:
* Must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy) or postmenopausal (defined as no menstrual cycle for at least 12 consecutive months).
2. For males:
* Must be surgically sterile, or compliant with a contraceptive method (effective barrier contraception, such as a condom with spermicide) during the study and then for at least 5 months (i.e., corresponding to 5 half-lives + 3 months) after the last dose of SKL35501.
* Must agree not to donate sperm during the study until 90 days after the last dose of SKL35501.
* Male patients with female partner(s) of childbearing potential:
* Female partner must use a highly effective method of contraception (e.g., oral contraceptives, IUD, diaphragm, etc.) during the study and 5 months (i.e., corresponding to 5 half-lives + 3 months) following the male patient's last dose of SKL35501.
* Male patients with female partner(s) of non-childbearing potential (i.e., postmenopausal or surgically sterile for at least 6 months prior to Screening):
* No additional contraception method is required.
11. Adequate hematologic and end-organ function, defined based on the following laboratory results obtained within (≤) 14 days prior to C1D1:
1. ANC ≥ 1.5 × 109/L (1500/μL), without G-CSF support. G-CSF may be administered until (\>) 14 days prior to C1D1.
2. Platelet counts ≥ 100 × 109/L (100,000/μL) without receiving any thrombopoietin receptor agonists, other therapies for thrombocytopenia or platelet transfusion for ≥ 14 days prior to C1D1.
3. Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused or receive erythropoietic treatment to meet this criterion until (\>) 14 days prior to C1D1.
4. AST and ALT ≤ 3 × ULN (≤ 5 × ULN for patients with documented liver metastases).
5. Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert's syndrome).
6. eGFR ≥ 60 mL/min (multiply the estimate of GFR by individual's BSA (calculated using an appropriate formula) and divide by 1.73 m2).
7. Albumin \> 28 g/L
Exclusion Criteria
Patients are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Patients with evidence of hydronephrosis.
2. History of solid tumor malignancy other than the diseases under study, diagnosed within (≤) the last 3 years of study enrollment, excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment).
3. History of ascites or pleural effusion, unless successfully treated, asymptomatic, and not requiring treatment for \> 2 months prior to C1D1.
4. History of and/or current cardiovascular events or conditions:
1. History of myocardial infarction, unstable or severe angina, or arterial thrombotic event (such as CVA or TIA) within (≤) 12 months prior to C1D1
2. Current NYHA stage II-IV congestive heart failure
3. Unstable arrhythmia, or history or presence of a clinically significant (in the Investigator's opinion) ECG abnormality
4. Screening QT (QTc) interval (average of triplicate measurements; corrected for heart rate using Fridericia's formula) \> 470 msec
5. Uncontrolled hypertension, defined as SBP \> 150 mm Hg and/or DBP \> 100 mm Hg at screening, despite optimal antihypertensive therapy.
5. Positive tests at screening for the following:
1. HIV: HIV patients on established ART for at least 4 weeks and have a viral load less than 400 copies/mL and CD4+ T-cell counts ≥350 μL may be eligible.
2. HBsAg: Patients with positive HBV test and HBV DNA \< 500 copies being treated with antivirals may participate.
i. HBcAb: Patients with a positive HBcAb test followed by a negative HBV DNA test at screening may be enrolled.
ii. HCV antibody test: Patients with a positive HCV antibody test followed by a negative HCV RNA test at screening may be enrolled.
6. Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding:
1. Patients with a history of DVT may participate if successfully treated, completely resolved, and no treatment has been given for \> 2 months.
2. Patients who suffered a thromboembolism \> 6 months prior and who are stable on anticoagulation may participate.
7. Uncontrolled diabetes.
8. Chronic severe liver disease or liver cirrhosis.
9. Any active or symptomatic persistent infection (bacterial, viral, or fungal) requiring systemic therapy within (≤) 14 days prior to C1D1.
10. Any psychiatric illness or social situation that would limit compliance with study requirements.
11. Any other significant co-morbidity, disease, metabolic dysfunction, physical examination, or clinical laboratory finding that contraindicates the use of an investigational drug, or may represent an unacceptable risk from treatment complications, or may affect adherence to the study procedures or the interpretation of the results.
Ineligible prior and ongoing treatment requirements:
12. Treatment with previous cancer therapies (including investigational cancer treatment) ≤ 28 days or 5 half-lives prior to C1D1, or radiation therapy within (≤) 4 weeks prior to start of SKL35502 (palliative radiation or stereotactic radiosurgery within (≤) 7 days prior to start of SKL35502). Patients must have recovered from all acute radiotherapy-related toxicities.
13. Prior radiopharmaceutical or radioligand therapy.
14. Patients who are receiving treatment with medications known to prolong the QT/QTc interval.
15. Live, attenuated vaccine within (≤) 28 days prior to C1D1, or anticipation of need for such a vaccine during the course of the study. COVID-19 vaccination is acceptable.
16. Any other therapy that is prohibited during the study. Refer to Section 6.9.1.
Other Exclusion Criteria:
17. Known hypersensitivity to SKL35502 or SKL35501 or any component(s) of SKL35502 or SKL35501.
18. Contraindications to or inability to perform the imaging procedures required in this study.
19. History of drug-induced anaphylactic or other severe hypersensitivity reactions.
20. History of any of the following: drug-induced SCAR; including but not limited to SJS/TEN, or DRESS syndrome), or dose-limiting immune-mediated reactions.
21. Current pregnancy and/or breast-feeding.
Safety and Preliminary Effectiveness of BNT317, an Investigational Therapy for Advanced Solid Tumors
BNT317, a bispecific antibody targeting PD-1 and CD39, is being tested alone or with standard-of-care chemotherapy in a first-in-human dose-escalation and expansion study in advanced solid tumors, including specific cohorts of relapsed/refractory clear cell renal cell carcinoma and second-line-plus HER2-negative gastric/GEJ adenocarcinoma.
NCT06750185 · Phase 1/2 · BioNTech SE
Recruiting sites: Kentucky, Michigan, North Carolina, Rhode Island, South Carolina, Texas
Read full eligibility criteria
If not specified otherwise, criteria listed below are applicable for all parts.
Key Inclusion Criteria:
* Have histologically or cytologically confirmed advanced tumors, who have failed standard therapy, or for whom no standard treatment option is available, or for whom standard therapy is not appropriate.
* Have at least one measurable lesion based on RECIST v1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system \[CNS\] metastasis should not be considered as a measurable lesion).
* Adequate hematologic and organ function, as defined in the protocol.
* Have had an adequate treatment washout period before randomization/enrollment, as defined in the protocol.
* Part B1 only: Histologically confirmed diagnosis of locally advanced, unresectable (not amenable to curative surgery or radiation therapy) or metastatic clear cell RCC (including those with sarcomatoid features).
* Part B1 2L subgroup only: Had disease progression during or after one line of prior anticancer therapy for recurrent/metastatic disease which must have included immune checkpoint inhibitor and/or tyrosine kinase inhibitor (TKI).
* Part B1 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following:
a. Prior treatment should also contain one or two of the following treatments:
* One line of immune checkpoint inhibitor.
* At least one line of a TKI.
* Part B2 only: Undergoing SoC treatment or is willing to start SoC treatment for 2L+ HER2-negative GC/GEJC in accordance with the product label and local treatment guidelines.
* Part B2 only: Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous cell carcinoma is excluded).
* Part B2 2L subgroup only: Had disease progression during or after one prior line of anticancer therapy for recurrent/metastatic disease which must have included a fluoropyrimidine analogue and a platinum agent with or without programmed death (PD)-1/ PD-ligand 1 (PD-L1). The total of cytotoxic containing regimens must be limited to maximum of 1 line for the recurrent/metastatic setting.
* Part B2 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following:
1. Prior treatment must include one line of treatment containing a fluoropyrimidine analogue and a platinum agent, unless the participant is not a candidate in the opinion of the treating physician.
2. Prior treatment should also contain one or two of the following treatments:
* One line of a cytotoxic agent per local SoC.
* One line of a non-cytotoxic agent alone or in combination with cytotoxic chemotherapy.
* Treatment with cytotoxic agents at the recurrent/metastatic setting must be limited to a maximum of two lines.
* Part B2 only: Have a helicobacter pylori status result determined and documented prior to trial screening as part of SoC.
* Part B3 only: Undergoing SoC treatment or is willing to start SoC treatment for 2L+ AGA-negative NSCLC in accordance with the product label and local treatment guidelines.
* Part B3 only: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC.
* Part B3 only: Have no actionable genomic alterations, such as Epidermal Growth Factor Receptor mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC.
* Part B3 only: Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.
* Part B3 only: Participants must have received 1 to 3 or more lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less.
Key Exclusion Criteria:
* Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:
* Any prior treatment which inhibits cluster of differentiation 39.
* Vaccination with live attenuated vaccine(s) within 4 weeks prior to the first dose of IMP.
* Any investigational product within 4 weeks or 5 half lives (if the half life of the other investigational product is known), whichever is longer, before the first dose of IMP in this study or ongoing participation in the active treatment phase of another interventional clinical study.
* Systemic cytotoxic chemotherapy, immunotherapy within 3 weeks or five half-lives of the chemotherapy (whichever is shorter) prior to the first dose of IMP.
* Radiation therapy (chest, brain or internal organs) within 4 weeks prior to the first dose of IMP.
* Palliative radiotherapy to metastasis within 2 weeks prior to the first dose of IMP.
* Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 2 weeks prior to the first dose of IMP. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) is allowed.
* Have any of the following CNS metastases:
* Untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm).
* Treated CNS metastases who are not neurologically stable or on steroids or anticonvulsants within 2 weeks before initiating IMP of this study.
* Brain metastases treated with radiotherapy that are not confirmed stable by magnetic resonance imaging or contrast-enhanced computer tomography 4 weeks after radiotherapy.
* Participants with known leptomeningeal metastases.
* Have uncontrolled hypertension or poorly controlled diabetes as specified in the protocol.
* Have a history of allogeneic hematopoietic stem cell transplantation or organ transplantation.
* Have a history of serious Grade ≥3 immune-related adverse events (irAEs) or irAEs that led to discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy may be included at the discretion of the investigator. If required by the investigator, after consultation with the sponsor.
* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma
This trial compares the combination of RAS(ON) inhibitors zoldonrasib (KRAS G12D-specific) plus daraxonrasib (pan-RAS inhibitor) versus gemcitabine and nab-paclitaxel chemotherapy as first-line treatment for metastatic KRAS G12D-mutated pancreatic adenocarcinoma.
NCT07805954 · Phase 3 · Revolution Medicines, Inc.
Recruiting sites: Arizona, Florida, Minnesota
Read full eligibility criteria
Inclusion Criteria:
* At least 18 years old and has provided informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Histologically or cytologically confirmed pancreatic adenocarcinoma, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
* No prior treatment in the locally advanced unresectable or metastatic setting
* Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
* Documented KRAS G12D mutation status.
* Measurable disease per RECIST v1.1.
* Adequate organ function (bone marrow, liver, kidney, coagulation).
Exclusion Criteria:
* Mutation status with known driver mutations for which there are approved targeted therapies.
* Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
* Tumors determined to originate from non-pancreatic primary sites.
* Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
* Active or known history of untreated central nervous system metastatic or leptomeningeal disease.
* Any conditions that may affect the ability to take or absorb study drug.
* Major surgery within 28 days prior to randomization.
* Patient is unable or unwilling to comply with protocol-required study visits or procedures.
* Additional inclusion \& exclusion criteria may apply.
Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer
This phase I trial tests the BET bromodomain inhibitor ZEN-3694 added to cetuximab (anti-EGFR antibody) plus encorafenib (RAF kinase inhibitor) in patients with BRAF V600E-mutant, refractory/relapsed metastatic colorectal adenocarcinoma.
NCT06102902 · Phase 1 · National Cancer Institute (NCI)
Recruiting sites: California, Colorado, Kansas, Louisiana, Ohio, Oklahoma, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically confirmed and radiographically measurable metastatic colorectal adenocarcinoma with known BRAF V600E mutation, confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory with at least one tumor measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and for which standard curative or palliative measures do not exist or are no longer effective
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with cetuximab and encorafenib in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Absolute neutrophil count ≥ 1,500/mcL
* Platelets ≥ 100,000/mcL
* Hemoglobin (Hb) ≥ 9 mg/dl
* Total bilirubin ≤ 1.5 mg/dl (excluding Gilbert's disease)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional upper limit of normal (ULN)
* Creatinine clearance (CrCL) glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Patients should be New York Heart Association Functional Classification of class II or better
* Patients must have progressed after at least 1 prior systemic treatment for incurable advanced or metastatic disease
* Patients must have received prior treatment with the combination of encorafenib and cetuximab. They must have tolerated the combination at doses planned for the study
* For the dose expansion phase, patients must have discontinued encorafenib at least 2 weeks prior to starting study treatment
* The effects of ZEN003694 on the developing human fetus are unknown. For this reason and because BRD and BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 4 months following the last dose of study drug. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to the start of investigational product. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or other agents used in study
* Patients with uncontrolled intercurrent illness including, but not limited to, active bleeding diatheses, poorly controlled infection/disorders, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used, either dose ZEN003694 2 hours before the H2 blocker or 10-12 hours after an H2 blocker. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Pregnant women are excluded from this study because ZEN003694 is BRD and BET inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study
Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial
Botensilimab (anti-CTLA-4) plus balstilimab (anti-PD-1) immune checkpoint inhibitors are being tested as neoadjuvant therapy prior to nephrectomy in patients with high-risk, non-metastatic clear cell renal cell carcinoma.
NCT07516366 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: California, Florida, Oklahoma, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Patients must have biopsy-confirmed, non-metastatic, high-risk renal cell carcinoma (RCC) with a clear cell component, defined as clinical stage T2N0, T3N0, T4N0, or any T stage with N1 disease (i.e., T2a-T4NanyM0 or TanyN1M0), and no evidence of metastatic disease
* Participants with resectable RCC are eligible, including those who have previously undergone surgical resection for RCC and subsequently developed resectable recurrent disease. Patients must be candidates for further curative-intent surgical resection. Prior systemic therapy for RCC (including VEGF-targeted therapy, immune checkpoint inhibitors, HIF-2α inhibitors, or other systemic anticancer therapies) is not allowed
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab in combination with balstilimab in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
* Patients must be considered suitable for curative-intent surgical resection of RCC, including radical or partial nephrectomy, as determined by the urology team and the treating physician according to standard clinical guidelines
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* Glomerular filtration rate (GFR) 50 mL/min (calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Also including a prior history of renal cell carcinoma
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Patients must be scheduled to undergo either partial or radical nephrectomy as part of treatment plan
* The effects of botensilimab and balstilimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of botensilimab and balstilimab administration. All patients of childbearing potential must undergo a blood or urine pregnancy test within 14 days prior to receiving the first dose of botensilimab and balstilimab to confirm they are not pregnant. If dosing is delayed beyond this window, the pregnancy test must be repeated to ensure results remain current
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
* Availability of pre-treatment archival slides or tissue blocks is required for inclusion in the study
Exclusion Criteria:
* Patients who have suspected or proven metastatic renal cell carcinoma
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab or balstilimab
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Pregnant women are excluded from this study because botensilimab and balstilimab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab or balstilimab, breastfeeding should be discontinued if the mother is treated with botensilimab or balstilimab
* Patients without a clear cell component in their baseline kidney biopsy or non-clear cell renal cell carcinoma (RCC) are excluded from this study
* Patients who have received prior treatment with an anti-PD-1, anti-programmed cell death protein ligand 1 (PD-L1), anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* Patients who have undergone major surgery within 28 days prior to the start of the study
* Patients with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug; the exception would be for syndromes which would not be expected to recur in the absence of an external trigger. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* Patients with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
* Patients with a baseline corrected QT interval (Fridericia's corrected QT interval \[QTcF\]) \> 480 ms on screening electrocardiogram (ECG), a history of congenital long QT syndrome, or clinically significant cardiac arrhythmias will be excluded
Total Pancreatectomy With Islet Autotransplantation (TPIAT) for High-Risk Patients With Pancreatic Tumors
This trial evaluates total pancreatectomy with islet autotransplantation, a surgical procedure removing the pancreas with reinfusion of isolated islet cells, in adults with periampullary neoplasms (including pancreatic adenocarcinoma) at high risk for pancreatic fistula after standard pancreaticoduodenectomy.
NCT07360119 · Phase N/A · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting sites: Maryland
Read full eligibility criteria
Inclusion Criteria:
* Adults aged 18 years and older.
* Patients with periampullary neoplasms requiring pancreaticoduodenectomy, including but not limited to:
* Pancreatic adenocarcinoma
* Distal bile duct adenocarcinoma
* Duodenal adenocarcinoma
* Leiomyosarcoma of the duodenum
* Pancreatic neuroendocrine neoplasms
* Ampullary adenoma
* Duodenal gastrointestinal stromal tumor
* High-risk intraductal papillary mucinous neoplasm according to Fukuoka criteria, specifically focal Intraductal Papillary Mucinous Neoplasm (IPMN) in the head of pancreas with high-risk stigmata or worrisome features on endoscopic ultrasound with fine-needle aspiration
* Mucinous cystic neoplasm
* Serous cystadenoma
* Soft pancreatic gland and main pancreatic duct ≤2 mm at the neck of the pancreas based on preoperative imaging.
* Adequate islet function with measurable C-peptide preoperatively to justify islet isolation and transplant.
Exclusion Criteria:
* Pregnancy.
* Active alcohol or illicit drug use.
* Poorly controlled psychiatric illness that limits ability to comply with care.
* Pre-existing insulin-dependent diabetes with absent C-peptide.
* Portal vein thrombosis or significant portal hypertension precluding islet infusion.
* Contraindications to major surgery.
* Body mass index greater than 35 kg/m².
A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy
Inavolisib (a PI3K inhibitor) plus fulvestrant versus alpelisib (also a PI3K inhibitor) plus fulvestrant is being studied in HR-positive, HER2-negative, PIK3CA-mutated locally advanced or metastatic breast cancer that progressed after CDK4/6 inhibitor plus endocrine therapy.
NCT05646862 · Phase 3 · Hoffmann-La Roche
Recruiting sites: California, Colorado, Connecticut, Florida, Georgia, Kentucky, Massachusetts, Michigan, Minnesota, New Jersey, North Carolina, Ohio, Oregon, Pennsylvania, Texas, Washington
Read full eligibility criteria
Inclusion Criteria for Main Study and Sub-study:
* If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
* Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
* Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
* Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test
* Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: \<= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapy in mBC setting allowed
* Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
* Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Life expectancy of \> 6 months
* Adequate hematologic and organ function prior to initiation of study treatment
Exclusion Criteria for both Main Study and Sub-study:
* Metaplastic breast cancer
* Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K/-AKT/-mTOR pathway
* Participant who relapsed with documented evidence of progression \> 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease
* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
* Inability or unwillingness to swallow pills
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Any history of leptomeningeal disease or carcinomatous meningitis
* Known and untreated, or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases are eligible if they meet specific certain criteria
* Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
* Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
* Requirement for daily supplemental oxygen
* Symptomatic active lung disease, including pneumonitis
* History of or active inflammatory bowel disease
* Any active bowel inflammation
* Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
* Participants with known human immunodeficiency virus infection that meet specific criteria
* History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence
* Chronic therapy of \>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
* Active ongoing osteonecrosis of the jaw
Exclusion Criteria for Main Study Only:
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
* Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day 1 of Cycle 1
* Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer
* Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations
* History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms
Exclusion Criteria for Sub-study Only:
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the substudy or within 2 weeks after the final dose of inavolisib and within 2 years after the final dose of fulvestrant, whichever is longer
* Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day -4 of Cycle 1
* Investigational drug(s) within 4 weeks prior to Day -4 or within 5 half-lives of the investigational drug(s), whichever is longer
* Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant formulations
* Treatment with mild, moderate, or strong inducers of CYP2B6, CYP3A4, and/or CYP2C19 (including St. John's Wort) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PK sample has been collected on Day 15 of Cycle 1
* Treatment with mild, moderate, or strong inhibitors of CYP2B6, CYP3A4, and/or CYP2C19 (including grapefruit juice or supplements) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PK sample has been collected on Day 15 of Cycle 1
A Study of Armored CAR T Cells in People With Cancer
DLL3-SAVVYZ-IL18 is a DLL3-targeted armored CAR T-cell therapy (co-expressing IL18) being studied in a phase 1 trial for DLL3-positive tumors, including small cell lung cancer and other neuroendocrine tumors, in patients who progressed after prior systemic therapy.
NCT07783477 · Phase 1 · Memorial Sloan Kettering Cancer Center
Recruiting sites: New Jersey, New York
Read full eligibility criteria
Inclusion Criteria:
Participant Inclusion: Collection of T cells (Part A)
* History of DLL3+ neuroendocrine tumors
* Includes patients with histologically confirmed SCLC, as well other advanced neuroendocrine tumors (NETs), including large cell neuroendocrine carcinomas (LCNECs), gastroenteropancreatic NETs (GEP-NETs), laryngeal NETs, genitourinary (GU) tract NETs, neuroendocrine prostate cancers (NEPCs), gynecological tract NETs, neuroblastomas, salivary NETs, skin NETs, NETs of unknown primary, or other tumor confirmed positive for DLL3 by IHC
* Any disease status is eligible for collection.
* DLL3 expression detected by IHC using archival tumor tissue or tissue obtained from a biopsy performed as part of standard clinical care. No new biopsy will be performed solely for DLL3 IHC eligibility testing.
* Off any immunosuppressive agents for 14 days prior to collection (physiologic dose of corticosteroids is acceptable)
Participant Inclusion: Treatment with DLL3-SAVVYZ-IL18 CAR T cells (Part B)
* Any participant with histologically confirmed SCLC or DLL3 positive tumor who has had one line of approved systemic therapy for limited or extensive stage disease and has progressed or is no longer deriving benefit or standard treatment is no longer tolerable or declines further standard treatment.
* Prior treatment should include an approved platinum-based regimen with/without ICI therapy if applicable to their disease.
* Other advanced tumors are eligible if there is documented progression and/or relapse after appropriate frontline treatment(s) and otherwise meet eligibility criteria.
* At least 1 measurable lesion as defined per modified RECIST 1.1 within 21 days prior to first dose of LDC.
* Age \> 18 years old at the time of signing the informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Minimum life expectancy of 12 weeks.
* Participants previously treated with DLL3-specific therapies (i.e. antibody-drug conjugates, T-cell engager molecules) are permitted.
* History of CNS metastatic disease is permitted if previously treated and stable, defined as no evidence of radiographic progression for at least 4 weeks prior to the first dose of LDC, with any neurologic symptoms returned to baseline. Asymptomatic CNS metastatic disease must also be radiographically stable for at least 4 weeks prior to the first dose of LDC.
* Adequate organ function is required, defined as follows:
* Hematologic: Hgb \> 9 g/dL, platelets \> 75 x103/ul
* Hepatic: Serum total bilirubin ≤1.5 mg/dL (unless Gilbert's syndrome), albumin \> 3 g/dL.
* Hepatic: ALT and AST \< 5 times the upper limit of normal unless thought to be disease-related.
* Renal: serum creatinine \< 2.0 mg/dL (\> 18 years) or ≤ 2.5 x institutional upper limit of normal (ULN) for age
* If serum creatinine is outside the normal range, then CrCl \> 40 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.73m2) \> 40% of predicted normal for age.
* Cardiac: LVEF ≥ 50% by resting echocardiogram
* Pulmonary: Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by pulse oximetry
Exclusion Criteria:
Participant Exclusion: Collection of T cells (Part A)
* Pregnant or lactating female participants; female participants of reproductive potential, unless they agree to use a highly effective method of contraception or abstain from heterosexual intercourse while receiving study treatment and for at least 12 months after all treatment is finished.
* Sexually active male participants with female partners of reproductive potential, unless they agree to use a condom during intercourse and their female partners use a highly effective method of contraception while the participant is receiving study treatment and for at least 12 months after all treatment is finished.
* Primary CNS malignancies, including glioblastoma multiforme (GBM), are excluded.
* Any systemic anti-cancer therapy within 14 days or at least 4 half lives prior to time of T cell collection, whichever is shorter.
* Radiation therapy completed within 7 days prior to time of T cell collection.
* Uncontrolled, symptomatic, intercurrent infection
* Patients with following cardiac conditions will be excluded:
* New York Heart Association (NYHA) stage III or IV congestive heart failure.
* Myocardial infarction ≤ 6 months prior to enrollment.
* Positive serologic test results for HIV.
* Patients with active hepatitis B infection (as manifested by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen)
* Patients with active hepatitis C infection (as manifested by detectable hepatitis C virus RNA by PCR)
Participant Exclusion: Treatment with DLL3-SAVVYZ-IL18 CAR T cells (Part B)
* For prior immune related adverse events (irAEs):
* Unresolved pneumonitis of any grade or history of any grade ICI-mediated CNS toxicities
* Other unresolved toxicity grade 2 or higher, excluding hypothyroidism.
* Any autoimmune disease requiring active systemic immunosuppression.
* Use of physiologic steroid replacement for adrenal insufficiency and inhaled corticosteroids are permitted
* Pregnant or lactating female participants; female participants of reproductive potential, unless they agree to use a highly effective method of contraception or abstain from heterosexual intercourse while receiving study treatment and for at least 12 months after all treatment is finished.
* Sexually active male participants with female partners of reproductive potential, unless they agree to use a condom during intercourse and their female partners use a highly effective method of contraception while the participant is receiving study treatment and for at least 12 months after all treatment is finished.
* Primary CNS malignancies, including glioblastoma multiforme (GBM), are excluded
* CNS metastatic disease that is symptomatic (including use of steroids within 7 days prior to the first dose of LDC) or new/enlarging is excluded. Patients with treated brain metastases are permitted if treatment was completed at least 4 weeks prior to the first dose of LDC and the disease has remained radiographically stable for at least 4 weeks prior to the first dose of LDC, with neurologic symptoms returned to baseline.
* Uncontrolled, symptomatic, intercurrent infection
* Patient/parent/guardian unable to give informed consent.
* Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study; conditions that in the Principal Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
A Study of GSK5764227 in Participants With Relapsed Small Cell Lung Cancer (SCLC) [EMBOLD SCLC-301]
Risvutatug rezetecan, a B7-H3-targeted antibody-drug conjugate with a topoisomerase inhibitor payload, is being compared to topotecan in patients with relapsed extensive-stage small cell lung cancer after prior platinum-based chemoimmunotherapy.
NCT07099898 · Phase 3 · GlaxoSmithKline
Recruiting sites: California, Florida, New York, North Carolina, Ohio
Read full eligibility criteria
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
* Adults \>18 or the minimum legal adult age at the time the informed consent form is signed
* Has histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).
* Has received 1 prior platinum-based systemic therapy with a PD- (L)1 inhibitor for at least 2 cycles of therapy and a chemotherapy free-interval of \>30 days, with documented progression. Participants with prior tarlatamab treatment in either the first- or second-line ES-SCLC setting are eligible.
* Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
* Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Has adequate organ function and an ECOG performance status of 0 or 1
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Pathological diagnosis of complex SCLC or transformed SCLC.
* Limited stage small cell lung cancer at diagnosis
* Has received any prior therapy with an Antibody-drug conjugate (ADC) with a Topoisomerase-1 (TOPO1)-inhibitor payload or treatments targeting B7-H3.
* Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Has severe, uncontrolled or active cardiovascular disorders.
* Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
* Known active infectious diseases requiring systemic treatment or known Human immunodeficiency virus (HIV).
* Has symptomatic brain metastases or untreated progression exclusively due to brain metastasis during or after the last treatment prior to screening, evidence of leptomeningeal/meningeal/brainstem metastasis or evidence of spinal cord metastases.
* Has any evidence of current interstitial lung disease or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high dose steroids.
* Has significant pulmonary disease or respiratory impairment (e.g., uncontrolled asthma/COPD, restrictive lung disease),
* Has active Hepatitis B or Hepatitis C
A Study of JNJ-98768111 in Participants With Advanced Prostate Cancer
JNJ-98768111 is an intravenously administered investigational agent whose mechanism of action is not stated in the registry, being studied in a phase 1 dose-finding and safety trial for advanced (metastatic, castration-resistant) prostate cancer that has progressed after prior AR-targeted therapy.
NCT07746713 · Phase 1 · Janssen Research & Development, LLC
Recruiting sites: Florida, Michigan, Utah
Read full eligibility criteria
Inclusion criteria:
* a. Histologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine features is permitted. b. Measurable or evaluable disease (metastatic prostate cancer) based on computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. Prior treatment with at least 1 prior novel androgen receptor (AR)-targeted therapy. c. Serum prostate-specific antigen (PSA) value greater than or equal to (\>=) 2 nanograms per milliliters (ng/mL). d. Prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to the first dose of trial drug and must continue this therapy throughout the treatment phase; e. Castrate levels of serum testosterone as defined in the protocol, prior to the first dose of trial intervention; f. Progressive metastatic disease following their most recent line of therapy. Disease progression will be defined by at least one of the following: PSA progression, radiographic progression according to response evaluation criteria in solid tumors (RECIST v1.1), or progressive bone disease according to prostate cancer working group 3 (PCWG3) criteria
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1
* Agree to all of the following during the trial and for 6 months after the last dose of trial drug: a. Use a highly effective method of contraception; b. Wear a condom when engaging in any activity that allows for passage of ejaculate to another person; c. Not to donate sperm or freeze for future use for the purpose of reproduction; d. Not plan to father a child. In addition, the participant should be advised of the benefit for a female partner to use a highly effective method of contraception
* Sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the trial and is willing to participate in the trial
Exclusion criteria:
* Active central nervous system (CNS) involvement
* Toxicity related to prior anticancer therapy that has not returned to Grade less than or equal to (\<=) 1 or baseline levels
* External beam radiation therapy to soft tissue lesions within 14 days prior to start of trial intervention
* History of clinically significant cardiovascular disease within 6 months prior to signing informed consent
* History of solid organ or bone marrow transplantation
A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors
KIN-2787 (exarafenib), an oral BRAF (Class I/II/III) kinase inhibitor, alone or combined with the MEK inhibitor binimetinib, is being studied in adults with BRAF- and/or NRAS-mutated advanced or metastatic solid tumors, including non-small cell lung cancer and melanoma.
NCT04913285 · Phase 1 · Pierre Fabre Medicament
Recruiting sites: California, Colorado, Florida, Minnesota, New Jersey, New York, Ohio, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Provide written informed consent prior to initiation of any study-specific procedures.
* Metastatic or advanced stage solid tumor
* Known BRAF Class I, Class II, or Class III alteration or melanoma with an NRAS mutation as confirmed by previous genomic analysis of tumor tissue or ctDNA.
* Measurable (Part A and B) or evaluable (Part A only) disease by RECIST v1.1.
* ECOG performance status 0-1
* Adequate organ function, as measured by laboratory values (criteria listed in protocol).
* Able to swallow, retain, and absorb oral medications.
Exclusion Criteria:
* Known participants who have received local therapy with either surgery and/or radiation therapy (participants with asymptomatic untreated brain metastasis may be eligible if met with certain criteria)
* In Part B Dose Expansion, previous treatment with any approved or in-development small molecule BRAF-, MEK-, or MAPK-directed inhibitor therapy.
* GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease.
* Active, uncontrolled bacterial, fungal, or viral infection.
* Participant with a positive test result for SARS-CoV2 infection, is known to have asymptomatic infection or is suspected of having SARS-CoV2, is excluded
* Women who are lactating or breastfeeding, or pregnant.
* Participants with any other active treated malignancy within 3 years prior to enrollment
Complete inclusion and exclusion criteria are listed in the clinical study protocol.
A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)
Rinzimetostat (ORIC-944, mechanism not stated in registry) combined with darolutamide is compared against physician's choice of ARPI (darolutamide or enzalutamide, androgen receptor antagonists) or docetaxel (a taxane microtubule inhibitor) in metastatic castration-resistant prostate cancer previously treated with abiraterone acetate.
NCT07723248 · Phase 3 · ORIC Pharmaceuticals
Recruiting sites: Florida, Indiana, Michigan, North Carolina, Ohio, South Carolina, Tennessee, Texas, Utah
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
* Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required
* Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function
Exclusion Criteria:
* Prior treatment for prostate cancer at any stage with cytotoxic chemotherapy, radioligand therapy (ie, 177Lu -PSMA-617, radium-223), ARPIs including apalutamide, darolutamide, and enzalutamide, PARP monotherapy or other systemic anticancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene or cell therapy, angiogenesis inhibitors, CDK4/6 inhibitors, PRC2 inhibitors) with the following exceptions:
1. Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure or disease progression occurred during treatment or within 3 months of treatment completion
* Any other anticancer therapy (drug or vaccine which does not meet exclusion criterion 1 above) within 28 days or 5 half-lives (whichever is longer) prior to randomization
* Known or suspected brain metastasis or active leptomeningeal disease
* Clinically significant cardiovascular disease defined as:
* Any medical (including active or clinically significant bacterial, fungal, or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the patient inappropriate for the study
* Active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery are excluded
Alternating Chemo-immunotherapy and FGFR Inhibitor for FGFR-positive Biliary or Cholangiocarcinoma
This phase II trial studies alternating chemo-immunotherapy (gemcitabine plus cisplatin chemotherapy with the PD-L1 antibody durvalumab) with the FGFR kinase inhibitor pemigatinib in patients with unresectable, locally advanced, or metastatic biliary tract cancer (including intrahepatic/extrahepatic cholangiocarcinoma, gallbladder, and ampulla of Vater carcinoma) harboring FGFR2 alterations.
NCT07780838 · Phase 2 · Ohio State University Comprehensive Cancer Center
Recruiting sites: Ohio
Read full eligibility criteria
Inclusion Criteria:
* Adults 18 years of age or older with histologically or cytologically confirmed unresectable locally advanced or metastatic carcinoma of the biliary tract, including intrahepatic and extrahepatic cholangiocarcinoma, gallbladder, and ampulla of Vater, at the time of diagnosis
* Patients must have tumors classified as having FGFR2 gene fusion/rearrangements or other gain-of function alterations involved in FGFR as detected by any analytically validated, Clinical Laboratory Improvement Act (CLIA)-certified molecular testing, including commercial tests (Foundation Medicine, Caris, Tempus, Guardant360, and others) or other platforms of next generation sequencing. Gene rearrangements are structural variants that can include inversions, translocations, duplications, and truncations. In addition, all patients will have tumor specimens sent and stored centrally
* Patients are permitted to have received one 21-day or 28-day cycle of either gemcitabine/cisplatin or gemcitabine/cisplatin with immunotherapy (either durvalumab or pembrolizumab) prior to inclusion in trial, and this will count as the first cycle in the schematic
* One or more measurable lesions per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients with ECOG performance status of 2 may be considered on a case-by-case basis by Principal Investigator
* Life expectancy of greater than 4 months
* Ability to understand and participate voluntarily, sign informed consent, and follow the study treatment plan and scheduled visits
* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3)
* Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
* Platelets ≥ 75 × 109/L
* Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
* Hemoglobin ≥ 90 g/L (9 g/dL)
* Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
* Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) are all ≤ 1.5 × upper limits of normal (ULN), with the exception of patients taking blood thinners with coagulation factor elevation associated with these drugs
* Serum bilirubin ≤ 1.5 × ULN (≤ 5 × ULN if the tumor involves the liver), unless associated with patient's primary cancer and/or metastases and with Principal Investigator's approval; biliary drains and stents are acceptable
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤ 3 × ULN (if with liver metastases, AST and ALT ≤ 5 × ULN), unless associated with patient's primary cancer and/or metastases and with Principal Investigator's approval; biliary drains and stents are acceptable
* Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula)
* Patients with an inherited cancer syndrome or a medical/family history suggestive of an inherited cancer syndrome are eligible
* Recovery from adverse events of previous systemic anti-cancer therapies to baseline or grade 1, except for:
* alopecia
* stable neuropathy of ≤ grade 2 due to prior cancer therapy
* Able to swallow and retain oral medication
* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks.
* They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression.
* For patients who have received chemotherapy in the previous one month, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.
* They must have an undetectable viral load and a CD4 count ≥ 250 cells/mcL within 7 days of enrollment.
* They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months. HIV-infected patients will be monitored every 12 weeks for viral load and CD4 counts
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of hepatitis B surface antigen \[HbsAg\]) are eligible
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
Exclusion Criteria:
* Received any definitive radiotherapy, targeted therapy, immunotherapy, or any investigational therapies within 13 days of the first study drug administration. Patients are permitted to have received one 21- or 28-day cycle of either gem/cis or gemcitabine/cisplatin/durvalumab prior to inclusion in trial, and this will count as the first cycle in the schematic. Localized palliative radiation therapy (should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
* Patients who have not recovered from reversible toxicity of prior anti-tumor therapy (except toxicities which are not clinically significant such as alopecia, grade 0-2 neuropathy)
* Patients who received prior FGFR-targeted therapy
* Within 2 weeks before the first dose of study drug, the subject's calcium and phosphate level continuing to exceed the ULN despite medical treatment
* Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis, or medical conditions that increase their risk of developing hyperphosphatemia or hypercalcemia
* History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung, with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
* Patients with clinically significant gastrointestinal dysfunction that may affect drug intake, transport or absorption (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
* Current evidence of corneal or retinal abnormalities that may increase eye toxicity, including but not limited to:
* Currently suffering from central serous retinopathy (CSR) or retinal vein occlusion (RVO), or with relevant history;
* Active wet age-related macular degeneration (wAMD);
* Diabetic retinopathy with macular edema;
* Uncontrollable glaucoma;
* Keratopathy, such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
* Consumed or anticipate consuming diet or drugs known to be strong or moderate cytochrome P450 (CYP) 3A4 inhibitors, strong CYP3A4 inducers or strong inhibitors of efflux transports including P-gp and BCRP for 28 days (or 5 half-lives, whichever is shorter) before the first dose of study drug or during the study drug treatment
* Patients with active or prior documented autoimmune or inflammatory disorders
* Participants must not have an active, known or suspected autoimmune disease which may affect vital organ function or has/may require systemic immunosuppressive therapy for management. Participants with inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]) are also excluded with the exception of the following: participants with type I diabetes mellitus, hypothyroidism (e.g. following Hashimoto syndrome) only requiring and stable on hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (such as celiac disease controlled by diet) are permitted to enroll. Patients without active disease for 5 years may also be enrolled after consultation with the study physician
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
* Systemic corticosteroids at physiologic doses not to exceed 10 mg of prednisone or its equivalent.
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Receipt of live attenuated vaccine within 30 days of planned start of study therapy.
* Note: Patients, if enrolled, should not receive live vaccine while receiving immunotherapy and up to 30 days after the last dose of immunotherapy
* Must not have prior history of organ transplantation, allogeneic transplantation, or double umbilical cord transplantation
* Active hepatitis B virus (HBV DNA \< ULN is required if HBs-Ag or HBc-Ab is positive), active hepatitis C, or uncontrolled HIV infection
* Known allergy or hypersensitivity to any study treatment
* Major surgery (thoracotomy, laparotomy, etc.) within 4 weeks or minor surgery (superficial skin surgery, lymphadenectomy, hernia repair, etc.) within 2 weeks before the first dose of study drug
* Patients with brain metastases or metastases elsewhere within the central nervous system (CNS) are excluded
* Patients with unresolved spinal cord compression
* Clinically significant, uncontrolled intercurrent illness including, but not limited to:
* Acute symptomatic or active infection requiring systemic therapy and medical intervention (e.g., IV antibiotics and/or hospitalization);
* Psychiatric illness and/or social situations that would limit compliance with completion of study requirements or ability to give informed consent
* Has a history of uncontrolled cardiovascular diseases including:
* Known New York Heart Association (NYHA) grade II or higher congestive heart failure, unstable angina pectoris, or myocardial infarction within 6 months before the first dose of study drug;
* Arrhythmias requiring treatment at screening;
* Left ventricular ejection fraction (LVEF) \< 50% at screening;
* Clinically significant prolonged QTc interval, or QTc interval \> 470 ms in women and \> 450 ms in men at screening;
* Cerebrovascular accident within 6 months before the first dose of study drug
* History of active bleeding within 6 months, signs of portal hypertension leading to gastric esophageal venous bleeding within 2 months before the first dose of study drug, or the investigator believes that there is uncontrolled bleeding (such as bleeding esophageal varices, local active ulcer lesions, etc.)
* At the investigator's discretion, with evidence of severe or uncontrolled systemic disease (such as unstable or non-compensatory lung, liver, or kidney disease); or any unstable systemic disease (including active clinically severe infections, uncontrolled hypertension, or liver, kidney, or metabolic disease)
* Pregnant or lactating women, as well as women with childbearing potential who are unwilling or unable to perform contraception from screening to 6 months after the last study drug administration; fertile men who are unwilling or unable to perform contraception from screening to at least 6 months after the last study drug administration
* History of another primary malignancy except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study or affect survival
* Any other medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
* History of hypovitaminosis D requiring supraphysiologic doses (e.g., 50,000 IU/weekly) to replenish the deficiency. Vitamin D supplements are allowed
B7-H3.CD28Z.CART in Solid Tumors
B7-H3.CD28Z.CART, an autologous CAR T-cell therapy targeting the B7-H3 antigen, is being studied (with fludarabine/cyclophosphamide lymphodepletion) in children and young adults with relapsed or refractory B7-H3-expressing pediatric solid tumors, including neuroblastoma.
NCT07358260 · Phase 1 · Robbie Majzner
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
Eligibility Criteria for Prescreening
Purpose of prescreening is to establish B7-H3 expression by IHC performed at Boston Children's Hospital. This can be performed at any time prior to completing the protocol screening process. Participants who meet the following criteria, will be offered participation in the full screening process and protocol enrollment, if eligible:
* Participants must have histologically confirmed diagnosis of a solid tumor that is relapsed or refractory for which standard curative measures do not exist or are no longer effective.
* Participant must have adequate pre-trial tumor material available to determine B7-H3 status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from the time of initial diagnosis is acceptable.
* Age \>=9 months and \<30 years.
* Lansky/Karnofsky performance status ≥50% (see Appendix A)
* Life expectancy of greater than 12 weeks
* Participants who are screened for this trial should be reasonably anticipated to meet the eligibility criteria for enrollment described in Section 3.2 if their tumor is B7-H3-positive.
* Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document for prescreening.
Eligibility Criteria for Enrollment The following criteria are required for initial study enrollment. Once enrolled, participants will need to meet specific criteria prior to lymphocyte apheresis, prior to the receipt of lymphodepletion chemotherapy and B7-H3.CD28Z.CART cell infusion as outlined in the Treatment Section of the Protocol.
Laboratory tests required for eligibility must be completed within 28 days prior to the date of registration. Disease evaluation is required only if needed for eligibility.
The screening window is 28 days.
* Participants must have histologically confirmed diagnosis of a solid tumor that is relapsed or refractory for which standard curative measures do not exist or are no longer effective.
* Participants must have measurable or evaluable disease for dose escalation. For expansion phase, participants with neuroblastoma must have measurable or evaluable disease by INRC. Participants with other solid tumors must have measurable disease by RECIST1.1 for the expansion phase.
* B7-H3 expression: Demonstration of B7-H3 expression with H score \>100 by immunohistochemistry (IHC) is required by IHC performed at Boston Children's Hospital. Participants may choose to enroll on the prescreening portion, which allows for assessment of B7-H3 expression only, prior to enrollment on the full clinical trial as described in Section 3.1.
* Age \>=12 months and \<30 years.
* Lansky/Karnofsky performance status ≥50% (see APPENDIX A: PERFORMANCE STATUS SCALES/SCORES)
* Life expectancy of greater than 12 weeks
* Prior therapy:
At enrollment these criteria do not apply to participants with available leukapheresis products; however, participants must meet all other eligibility criteria and meet criteria to start lymphodepleting chemotherapy as outlined in Section 5.4.1.
Participants must have received prior radiation therapy and/or chemotherapy and recovered from all acute treatment-related toxicities of prior therapy prior to entering this study. There is no upper limit to the number of prior therapies allowed. Participants must be:
* At least 1 week post any small port radiation therapy; at least 6 weeks from large field or other substantial bone marrow irradiation (craniospinal, whole abdomen, total lung, total body irradiation, \>50% marrow).
* At least 2 weeks since any prior myelosuppressive chemotherapy
* At least 28 days from other investigational antineoplastic or disease-directed agents
* At least 7 days from most recent myeloid growth factor, at least 14 days must have elapsed after receipt of pegfilgrastim.
* At least 7 days from prior biologic antineoplastics, tyrosine kinase inhibitor, targeted agent or metronomic non-myelosuppressive chemotherapy.
* At least 21 days or 5 half-lives, whichever is shorter, post any treatment with monoclonal antibodies (including checkpoint inhibitors and bevacizumab)
* At least 7 days from dinutuximab treatment
* At least 8 weeks from prior cellular therapy or vaccine therapy with recovery of associated toxicities. If prior CAR T cells, need documented lack of persistence of prior product.
* At least 6 weeks post 131I-MIBG therapy or other radioisotope therapy
* At least 6 weeks post autologous stem cell therapy infusion following myeloablative conditioning
* Participants can be eligible after autologous stem cell infusion without myelosuppressive therapy at any time as long as other criteria are met.
* At least 12 weeks post allogeneic stem cell transplant with no evidence of GVHD or ongoing toxicities.
* Steroid use: Corticosteroids at or below physiologic doses (replacement therapy for management of pituitary/adrenal insufficiency) is allowed and/or topical administration (e.g. inhaled or dermatologic) is allowed. Hydrocortisone for blood product premedication is allowed.
* Participants must have normal marrow function as defined below: Values must be without transfusions or platelet growth factor within 7 days. Participants with known marrow involvement are exempt from these requirements.
* hemoglobin ≥7.0g/dL
* absolute neutrophil count ≥750/mcL
* platelets ≥75,000/mcL
* Adequate renal function defined as creatinine below normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \<18yo) ≥70mL/min/1.73m2
* Maximu Serum Creatinine (mg/dL)
* 6 months to 1 year: MALE = 0.5 FEMALE = 0.6
* 1 year \< 2 years: MALE = 0.6 FEMALE = 0.6
* 2 year \< 6 years: MALE = 0.8 FEMALE = 0.8
* 6 years \< 10 years: MALE = 1 FEMALE = 1
* 10 years \< 13 years: MALE = 1.2 FEMALE = 1.2
* 13 years \< 16 years: MALE = 1.5 FEMALE = 1.4
* ≥16 years: MALE = 1.7 FEMALE = 1.4
* Adequate hepatic function
* Serum ALT/AST \<3.0X ULN
* Total bilirubin \< 3X ULN, except in participants with confirmed Gilbert's syndrome, where direct bilirubin must be \<3X ULN.
* Adequate cardiac function
* Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography
* Adequate pulmonary function
* No evidence of dyspnea at rest
* No exercise intolerance due to pulmonary insufficiency
* Pulse oximetry \>92% while breathing room air
* Females of childbearing potential must have a negative serum or urine pregnancy test
* The effects of B7-H3.CD28z.CART on the developing human fetus are unknown. For this reason and because other chemotherapeutic agents used in the study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study, and for 1 year after receiving the preparative lymphodepletion regimen or for as long as B7-H3.CD28z.CARTs are detectable in peripheral blood. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, and for 1 year after receiving the preparative lymphodepletion regimen or for as long as B7-H3.CD28z.CARTs are detectable in peripheral blood.
* Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document. Pediatric patients will be included in the consent discussion as age-appropriate and will provide written informed assent as applicable per institutional standard.
Exclusion Criteria:
* Participants who are receiving any other investigational agents.
* Participants with known current brain metastases or leptomeningeal disease. Prior CNS metastatic disease is allowable if prior resection and/or radiation occurred at least 8 weeks prior to enrollment, without any intervening CNS metastasis, progression or recurrence, and participants are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities.
* Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids/ immunosuppressive medication/ disease modifying agents within the last 2 years
* Prior solid organ transplant. Prior allogeneic or autologous stem cell transplant is permitted as outlined in Section 3.2.
* Active or uncontrolled viral, bacterial or fungal infection. Participants may be receiving ongoing therapy for controlled infection.
* Participants with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years.
* CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgement of the investigator may impair the ability to evaluate neurotoxicity.
* History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agents used in the study or in the manufacturing of cells.
* HIV/HBV/HCV infection: Participants are required to be negative for HIV Antibody or HIV viral load, negative for Hepatitis surface antigen (HbsAg) or viral load and negative for HCV antibody or HCV viral load. These participants are ineligible because of the potential for in vivo retroviral recombination events that could lead to replication-competent γ-retrovirus. A history of HIV, Hepatitis B, or Hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because the effects of B7-H3.CD28Z.CART cells on the developing fetus are unknown and because chemotherapeutic agents with the potential for teratogenic or abortifacient effects are used in this study. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with B7-H3.CD28Z.CART cells and chemotherapy, breastfeeding should be discontinued if the mother is treated with T cells on this study (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Decitabine/Cedazuridine (INQOVI), an Oral DNA Demethylating Agent, in Subjects With BAP1 Cancer Predisposition Syndrome and Subclinical, Early-Stage Mesothelioma
Oral decitabine/cedazuridine (a DNA demethylating agent) is being studied as treatment for subclinical, early-stage mesothelioma in patients with BAP1 cancer predisposition syndrome who are not yet candidates for standard front-line therapy.
NCT05960773 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: Maryland
Read full eligibility criteria
* INCLUSION CRITERIA:
* Participants with history of germline BRCA1-Associated Protein-1 (BAP1) mutations.
* Histologically confirmed by NCI LP subclinical, early-stage (Tx-T1) mesotheliomas.
* Participants with other early-stage BAP1-associated malignancies in addition to subclinical, early-stage mesotheliomas are eligible for study.
* The extent of the disease (Tx by radiographic imaging) must be insufficient to warrant approved front-line therapies (surgery, chemotherapy, immunotherapy) per standard of care (SOC). Participants with cT1 tumors may be eligible for study if they have been offered and have refused front-line SOC treatment.
* Age \>= 18 years.
* Evaluable disease as confirmed by minimally invasive (videoscopic) assessment (thoracoscopy and/or laparoscopy) performed at screening (within 8 weeks prior to treatment initiation).
* Willingness to undergo pre- and post-treatment minimally invasive thoracoscopy and/or laparoscopy to assess treatment response.
* Willingness to co-enroll on 20C0106 (Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients with BAP1 Tumor Predisposition Syndrome) and/or 06C0014 (Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) to enable collection/processing of tumor, blood and normal pleura if applicable per PI.
* ECOG performance status 0 - 1
* Adequate pulmonary reserve evidenced by FEV1 and DLCO \>= 35% predicted on screening pulmonary function testing (PFTs).
* Oxygen saturation \>= 92% on room air by pulse oximetry at screening.
* Adequate renal, hepatic, and hematopoietic function at screening as defined below:
* leukocytes \>= 3,000/microL
* absolute neutrophil count \>= 1,500/microL (without transfusion or cytokine support within 2 months prior to study treatment initiation)
* absolute lymphocyte count \> 800/microL
* platelets \>=100,000/microL and \< 1,200,000/microL
* prothrombin time (PT) \<=2 seconds above the upper limit of normal (ULN)
* total bilirubin \< 1.5 X institutional upper limit of normal OR direct bilirubin \<= 1 ULN for participants with total bilirubin \> 1.5 ULN
* serum albumin \>= 2.0 mg/dL
* aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<= 2.5 X institutional ULN
* creatinine \<= 1.6 mg/ml OR creatinine clearance (eGFR) \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.
* Individuals of child-bearing potential (IOCBP) and those that can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization) from the study entry and up to 6 months (IOCBP) or 3 months (those that can father children) after the last dose of the decitabine/cedazuridine.
* Nursing (including breastfeeding) participants must be willing to discontinue nursing from study treatment initiation through 2 weeks after the last dose of the study drug.
* The ability of a participant to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
* Participants with cancers requiring frontline standard of care treatment.
* Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to study treatment initiation), myocardial infarction (\< 6 months prior to study treatment initiation), unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II, serious cardiac arrhythmia, clinically significant bleeding or clinically significant pulmonary embolism.
* Therapeutic anticoagulation within 2 weeks prior to study treatment initiation.
* Active Hepatitis A (HAV), Hepatitis B (HBV) (e.g., HBsAg reactive), or Hepatitis C (HCV) (e.g., HCV RNA \[qualitative\] is detected) at screening.
* History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
* Other active infections requiring systemic therapy.
* Active COVID infection.
* Major surgery within 4 weeks prior to study treatment initiation.
* Immunosuppressive medications within 4 weeks prior to study treatment initiation except non-systemic corticosteroids.
* History of prior treatment with a DNA demethylating agent.
* Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in IOCBP at screening).
* Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer
Intratumoral injection of MMR (measles, mumps, rubella) vaccine, delivered via endoscopic ultrasound guidance into the tumor, is being studied in borderline resectable/unresectable non-metastatic pancreatic cancer following completion of standard chemotherapy and radiation therapy.
NCT07539155 · Phase 1/2 · University of Arkansas
Recruiting sites: Arkansas
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥ 18 years.
2. Pathologically proven locally advanced adenocarcinoma of pancreas.
3. Borderline resectable pancreatic cancer that is determined to be unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following:
1. Encasement of gastroduodenal artery up to the common hepatic artery/short segment encasement or abutment of the hepatic artery, but without extension to the celiac trunk.
2. Venous involvement of SMV or portal vein, less than 180 degrees.
3. Tumor abutment of SMA, less than half the circumference of the vessel wall. OR
Unresectable pancreatic cancer that remains unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following:
4. Greater than 180-degree encasement or occlusion/thrombus of SMA, unresectable SMV, or SMV-portal confluence occlusion.
5. Direct involvement of inferior vena cava, aorta, celiac trunk, or hepatic artery, as defined by the absence of fat plane between low-density tumor and these structures on CT scan.
OR Surgeon deems that the pancreatic cancer is unresectable.
4. Prior history of treatment with chemotherapy (e.g., FOLFIRINOX, Gemcitabine + Abraxane or NALIRIFOX \[liposomal irinotecan (Nal-IRI or Onivyde®), Nab Paclitaxel, 5 fluorouracil (5-FU)/leucovorin and oxaliplatin\]) and RT. The chemotherapy regimen is per treating physician's choice. The chemotherapy agent for radio sensitization is up to the treating physician (capecitabine, 5FU or gemcitabine).
a. The chemo-radiation therapy regimen should be completed at least 6 weeks but no more than 12 weeks from planned Day 1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Adequate hematological function (Hemoglobin \> 9g/dL, White Blood Cell (WBC) count \> 1500 K/µL, Absolute Neutrophil Count (ANC) \> 500 K/µL, Platelet count \> 100 K/µL).
7. Adequate hepatic function (Total bilirubin ≤ 1.5 x institutional upper limit of normal \[ULN\]) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 × ULN, subject is eligible); Aspartate aminotransferase (AST\[SGOT\]) or Alanine aminotransferase (ALT\[SGPT\]) ≤ 2.5 × institutional ULN; Serum albumin ≥ 3.0 g/dL.
8. Adequate renal function (i.e., creatinine less than 1.5 times ULN).
Exclusion Criteria:
1. Pancreatic cancer that was either resectable before SoC treatment or became resectable following SoC chemotherapy and RT.
2. Subjects with radiographically proven metastatic disease are excluded.
3. Subject must not be pregnant and/or currently breastfeeding or plan to be.
4. Subject must not have received any live vaccine, including MMR, within 30 days prior to the dose of study drug.
5. Subject must not have treatment with any anti-cancer therapy including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents, within 5 half-lives (or 2 weeks if half-life is unknown) prior to day 1.
6. Subject has no unresolved toxicities, AEs ≥ Grade 2 (NCI CTCAE version 5.0), from prior anticancer therapy.
7. Any other condition that, in the opinion of the investigator, might interfere with the safe conduct of the study.
Perioperative FLOT(D) With Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Esophageal Cancer
This phase 1 trial adds personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) to perioperative FLOT chemotherapy (5-FU, leucovorin, oxaliplatin, docetaxel) plus durvalumab immunotherapy in patients with resectable esophageal or gastroesophageal junction adenocarcinoma.
NCT07700420 · Phase 1 · University of Texas Southwestern Medical Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. At least 18 years of age at date of enrollment. Both men and women and members of all races and ethnic groups will be included.
2. Willing and able to provide written informed consent.
3. Pathologic diagnosis of esophageal or gastroesophageal junction adenocarcinoma. GEJ cancer includes Siewart types 1 and 2 tumors. Siewart type 3 is also eligible as long as the patient is intended to be treated in the same way as for type 1 and 2 tumors (i.e. candidate for FLOT-(D), resectable, amenable to radiation)
4. T1N+ or T2-4N(any) by the American Joint Committee on Cancer staging manual 8th edition
5. Primary tumor (and lymph nodes) that appear to be resectable in the opinion of an experienced thoracic surgeon or surgical oncologist 19.
6. Measurable disease by RECIST 1.1 is not a requirement in order to enroll on this study. Those who have measurable disease at baseline will be followed by RECIST 1.1 criteria at time of restaging.
7. Primary tumor (and applicable nodal sites) that appears amenable to radiation in the opinion of an experienced radiation oncologist.
8. Eastern cooperative Oncology Group (ECOG) performance status of 0-1
9. No prior systemic treatment or radiation for esophageal/GEJ adenocarcinoma. Patients who have received prior endoscopic therapies with subsequent recurrence necessitating curative-intent surgery will be eligible for enrollment.
10. Adequate organ and marrow function as defined below:
10.0 ANC ≥1500/mL 10.1 Platelet ≥100,000/mL 10.2 Total Bilirubin ≤ 1.0 x the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
10.3 AST and/or ALT both ≤ 1.5x ULN with alkaline phosphatase ≤2.5x ULN 10.4 Creatinine Clearance ≥ 30 mL/min by Cockroft Gault
11. All men, as well as women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of radiation through 120 days after completion of adjuvant chemotherapy or immunotherapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
11a. A woman of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
1. Patients with adenosquamous cell carcinoma, squamous cell carcinoma, GI stromal tumor, or neuroendocrine tumor (any grade) of the esophagus or GEJ.
2. Receipt of prior chemotherapy, radiotherapy, or both for esophageal or gastroesophageal junction cancer (any type).
3. Any other active malignancies besides localized skin cancers or in situ carcinomas. Patients with localized prostate or breast cancers who have been stable for ≥ 6 months on adjuvant therapy without evidence of active disease will be eligible to enroll on this study. Patients with a history of cancer that has not been active in the last 5 years may be included but only after consultation with the principal investigator.
4. Prior RT to the chest or abdomen (not esophagus/GEJ) that would, in the opinion of a radiation oncologist, limit the safety of PULSAR.
5. Known dihydropyrimidine dehydrogenase (DPYD) intermediate or poor metabolizer phenotype where administration of full dose 5-fluoruracil would be prohibitively toxic. It is not a requirement to test DPYD deficiency prior to enrollment. Patients found to be DPYD intermediate or poor metabolizers through the course of standard of care evaluation will be removed from the protocol and followed for DLTs. These patients will be replaced.
6. Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements or that would be prohibitive of a surgical resection in the opinion of a surgical oncologist or thoracic surgeon.
7. Chemotherapy, or other systemic cancer therapy for non-esophageal or GEJ cancer within 52 weeks prior to starting study treatment (with the exception of long-term adjuvant therapy for curative-intent prostate or breast cancer, as defined above).
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to FLOT chemotherapy, durvalumab or other agents used in study.
9. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
10. Unwilling or unable to undergo placement of chest wall mediport for chemotherapy administration.
11. Any autoimmune condition requiring immunosuppression beyond physiologic doses of steroids will not be eligible for receipt of durvalumab. Patient would still be eligible for enrollment for receipt of perioperative FLOT only and can enroll on this study while receiving FLOT.
12. Requirement of prednisone 10 mg (or prednisone equivalent) or more daily for any reason (Inhalational steroids for chronic obstructive pulmonary disease, asthma, or the like, is allowable). Patient would still be eligible for enrollment for receipt of perioperative FLOT only if they are meeting all other eligibility criteria.
13. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
Ph II Intraperitoneal Paclitaxel + System Therapy in GI Ca w/Peritoneal Carcinomatosis (STOPGAP-B)
This phase II basket trial evaluates intraperitoneal plus systemic paclitaxel chemotherapy (administered IP-IV every 2 or 3 weeks) in patients with gastrointestinal adenocarcinomas (gastric/gastroesophageal, colorectal/appendiceal, small bowel, or hepatobiliary) complicated by peritoneal carcinomatosis.
NCT07795749 · Phase 2 · University of California, Irvine
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Cohort A: Patients must have histologically or cytologically confirmed primary gastric or gastroesophageal adenocarcinoma with a clinical diagnosis of metachronous PC with a history of prior gastric cancer resection. Extraperitoneal metastases are allowed.
* Cohort B: Patients must have histologically or cytologically confirmed primary colorectal or appendiceal adenocarcinoma with PC . Extraperitoneal metastases are allowed. Patients with PC amenable to cytoreductive surgery (CRS) without the need for upfront systemic therapy as determined by a peritoneal malignancy surgeon within 4 weeks prior to enrollment are excluded.
* Cohort C: Patients must have adenocarcinomas of the digestive tract with PC not included in Cohorts A and B (including but not limited to carcinomas of the small bowel and hepatobiliary tract).
* Must have peritoneal cytology positive disease or peritoneal carcinomatosis detected by imaging, laparoscopy or laparotomy
* Age ≥ 18
* Performance status: ECOG performance status ≤ 2 (Appendix A) . ECOG 2 allowed if attributed to malignancy (rather than comorbidities)
* Life expectancy of greater than 3 months
* Adequate organ and marrow function as defined below: Leukocytes: ≥ 2,000/mcL; Absolute neutrophil count: ≥ 1,500/mcL (may receive gcsf); Platelets: ≥ 70,000/mcl (may receive TPO); Total bilirubin: within 2x of normal institutional limit; AST(SGOT)/ALT(SPGT): ≤5 X institutional upper limit of normal; Creatinine: \< 2 X institutional upper limit of normal; Hemoglobin: Hemoglobin \> 8.0 g/dL (may be transfused); Serum albumin: ≥ 2.5 g/dL
* Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
* Any evidence of small or large bowel obstruction with the exception of gastric outlet obstruction due to primary malignancy
* Uncontrolled intercurrent illness including, but not limited to, the following conditions: Ongoing or active infection; Symptomatic congestive heart failure; Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event,) within 3 months before initiation of treatment; Unstable angina pectoris; Cardiac arrhythmia
* History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ and not treated with systemic therapy.
* History of prior iterative intraperitonealtherapy administered either as HIPEC, PIPAC or NIPEC. Single exposure to HIPEC at the time of cytreduction is not an exclusion
* Inability to comply with study and follow-up procedures as judged by the Investigator
* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Has an active infection requiring systemic therapy.
* Prior surgery that would preclude safe diagnostic laparoscopy and port placement
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Short Course ADT for High Risk Low/Intermediate Risk ARTERA Prostate Cancer
This trial studies short-course (6-month) androgen deprivation therapy combined with dose-escalated radiotherapy (SBRT with or without brachytherapy boost) in high-risk (with low/intermediate ARTERA AI score), node-negative, localized prostate cancer without prior treatment.
NCT07801664 · Phase 2 · NYU Langone Health
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
* Ability to understand and willingness to sign a written informed consent document
* 18 years of age or older male participants
* Biopsy proven prostate cancer meeting at least one of the following high-risk criteria: Gleason score 8-10 OR; Baseline PSA \>20 up to and including 40 ng/ml OR; Patients with Gleason score 6-7 remain eligible if the PSA criterion (\>20 ng/mL) is met OR; MRI Radiographic stage T1-T3 disease without evidence of nodal involvement
* No imaging evidence of nodal metastases on baseline MRI/ CT of the pelvis and PET-PSMA scans
* Low risk or intermediate risk ARTERA AI scores
* Serum testosterone ≥ 120 ng/dL determined prior to ADT start
* At least 4 weeks must have elapsed from major surgery
* Karnofsky Performance Status (KPS) \> 80
* Prostate size \< 90 cc
* MRI findings: Lesion may have extracapsular extension (ECE)
* International Prostate Symptom Score (IPSS) \< 22
* Satisfy all MRI screening criteria and be willing to fill out the standard MRI screening form
Exclusion Criteria:
* Gleason score 6 or 7 in the absence of PSA \>20 ng/mL
* PSA \>40 ng/mL
* Prior or concurrent androgen deprivation therapy for prostate cancer of \>3 months duration
* High Risk ARTERA scores
* MRI findings: suspicious nodal metastases
* Evidence of regional lymphadenopathy or metastatic disease on MRI/CT or PSMA PET scan
* Metallic implant or device in the pelvis that might distort the local magnetic field and compromise quality of mp-MRI
* Contra-indications to receiving gadolinium contrast
* KPS \< 80
* Pelvic or Prostate MRI or CT (MRI preferred) evidence of radiographic T4, or N1 disease or bone disease
* Prior treatment for prostate cancer, including history of chemotherapy or surgery for prostate cancer (except for prior \[transurethral resection of prostate\] TURP or greenlight \[photo selective vaporization of prostate\] PVP which would be allowed)
* History of another malignancy within the previous 2 years except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, currently in complete remission, or any other cancer that has been in complete remission for at least 3 years. Patients with Crohn's disease or ulcerative colitis
* IPSS \> 22
* Currently on any ARPis (including but not limited to: enzalutamide, apalutamide, darolutamide, or abiraterone)
* Prior pharmacologic androgen deprivation therapy (ADT) for prostate cancer is permitted under the following (2) conditions: 1) Participants meeting this criterion will be assigned to a separate stratum within each primary treatment cohort. 2) Patients remain eligible for enrollment provided they have received no more than 3 months of ADT in total, regardless of whether ADT was initiated before screening or registration.
THIO and Cadonilimab in Resectable Hepatocellular Carcinoma
This trial evaluates ateganosine (THIO, mechanism not stated in the registry) combined with cadonilimab (an anti-PD-1/L1-related immune checkpoint agent) as neoadjuvant treatment in patients with resectable hepatocellular carcinoma prior to curative-intent surgery.
NCT07446257 · Phase 1 · University of Texas Southwestern Medical Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Diagnosis of HCC confirmed by histology or according to the American Association for the Study of Liver Disease (AASLD) criteria
a. Availability of tumor tissue samples prior to the first day of study treatment is required for all patients.
2. HCC that is amenable to R0 resection with curative intent as determined by treating surgical/medical oncologists in consultation with the principal investigator. Subject must be a suitable candidate for surgery based on evaluations by the treating surgeon/oncologist.
3. Measurable disease according to RECIST 1.1
4. No prior anti-PD (Programmed death)-1/L1 therapies for any indication
5. Age ≥18
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
7. Child Pugh A
8. Adequate organ and marrow function as defined below:
1. ANC (absolute neutrophil count) ≥ 1.5 x 109/L (does not apply to patients with benign ethnic neutropenia)
2. Platelets ≥ 75 x 109/L without transfusion
3. Hemoglobin ≥ 9 g/dL without transfusion within 2 weeks of screening
4. ALT (Alanine Aminotransferase) ≤ 3 2 x ULN (Upper Limit of Normal)
5. Bilirubin ≤ 3 x ULN
6. Creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault formula using actual body weight
9. All etiologies of chronic liver disease including but not limited to Hepatis C Virus (HCV) or Hepatis B Virus (HBV) infection. HCV and HBV infection status does not preclude eligibility as long as patients meet all other eligibility criteria but must be known prior to starting treatment. Patients with HBV must be on anti-viral therapy prior to the first day of investigational drug treatment. Patients with HCV may include active or resolved infection.
10. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following the last dose of ateganosine or 4 months following the last dose of cadonilimab. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
11. Ability to understand and the willingness to sign a written informed consent.
12. Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion Criteria:
1. Presence of extrahepatic extension of disease
2. Prior locoregional therapy to target lesions is not allowed. History of curative locoregional therapy is allowed provided the following are met: 1) previously treated tumor is not viable without evidence of residual disease for at least 12 months, and 2) patient has not received local therapy in the past 12 months.
3. Known fibrolamellar HCC or combined HCC-cholangiocarcinoma histology
4. History of hepatic encephalopathy
5. Severe ascites requiring paracentesis in the past 3 months
6. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study
7. Prior significant bleeding event in the past 3 months that may pose a surgical risk
8. History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure)
9. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to:
1. Autoimmune interstitial lung disease (lymphangitic spread of cancer is not disqualifying or stable/chronic lung disease that is not likely to be autoimmune in nature and progressive),
2. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs,
3. Clinically significant cardiovascular disease,
4. A condition that may obscure the interpretation of toxicity determination or AEs,
5. History of prior bone marrow and/or solid-organ transplantation
10. Hypersensitivity to IV contrast; not suitable for pre-medication
11. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past year (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), with the following exceptions:
1. Autoimmune diseases with only dermatologic involvement such as eczema, vitiligo, lichen chronicus, or resolved childhood asthma/atopy which involves less than 10% of the body surface area and symptoms are well controlled on topical treatments without recent exacerbations requiring other therapies
2. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency) is not considered a form of systemic treatment
3. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study
12. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses ≤10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease.
13. Prior malignancy that required systemic treatment within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Patients with a cancer history with a low risk of recurrence or progression may be enrolled as determined by the principal investigator.
14. Prisoners or subjects who are involuntarily incarcerated
15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG (Human chorionic gonadotropin) laboratory test
16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
17. Evidence of bleeding diathesis or significant coagulopathy
18. Current use of full dose anticoagulant use which cannot be temporarily discontinued for surgery
19. Receipt of live vaccinations within 30 days of first treatment day
A Study of Neoadjuvant Amivantamab With Either Lazertinib or Chemotherapy in Participants With Resectable EGFR-Mutated NSCLC
Neoadjuvant amivantamab (an EGFR/MET-targeted bispecific antibody, per Janssen's known regimen but here described as administered biologic) combined with either lazertinib or carboplatin/pemetrexed chemotherapy is being studied in patients with resectable, EGFR-mutated Stage II-IIIB non-small cell lung cancer prior to surgery.
NCT07586202 · Phase 2 · Janssen Research & Development, LLC
Recruiting sites: California, Oregon
Read full eligibility criteria
Inclusion Criteria:
* Participant must have histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) with completely resectable Stage II-IIIB N2 disease
* Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multidisciplinary team evaluation
* Participant must consent to a screening biopsy, if clinically feasible, if no adequate tumor tissue is available for a baseline sample
* Participant may have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor
* Have an eastern cooperative oncology group (ECOG) performance status of 0 or 1
Exclusion Criteria:
* History of uncontrolled illness
* Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current interstitial lung disease (ILD)/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Suspected or known allergies, hypersensitivity, or intolerance to excipients of: the combination of amivantamab and lazertinib or carboplatin and pemetrexed
* Presence of primary driver mutations (anaplastic lymphoma kinase \[ALK\], mesenchymal-epithelial transition \[MET\], human epidermal growth factor receptor 2 \[HER2\], proto-oncogene tyrosine-protein kinase ROS \[ROS1\], neurotrophic tyrosine receptor kinase \[NTRK\], B-Raf proto-oncogene \[BRAF\], REarranged during transfection \[RET\], or kirsten rat sarcoma viral oncogene homolog \[KRAS\]) , besides EGFR Exon 19del or Exon 21 L858R mutations, as determined by local genomic testing
* Prior treatment with any systemic anti-cancer therapy for NSCLC including EGFR-tyrosine kinase inhibitor (TKI) therapy, chemotherapy, biologic therapy, immunotherapy, or any investigational drug
A Study on How to Safely Guide Surgery for Melanoma and Similar Skin Tumors in Children Using Pathology and Genetic Information
This trial tests a risk-based surgical management strategy—using pathology and genetic risk stratification to determine extent of excision and need for sentinel lymph node biopsy—versus standard surgical approach in children and young adults with newly diagnosed, localized cutaneous melanoma or atypical Spitz/Spitzoid melanocytic tumors.
NCT07621614 · Phase 2 · Children's Oncology Group
Recruiting sites: California, Delaware, Florida, Ohio, Pennsylvania, Tennessee, Texas, Utah
Read full eligibility criteria
Inclusion Criteria:
* Patients ≤ 25 years old
* Newly diagnosed localized cutaneous melanoma, atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasm by local institution pathology report
* Patients must have disease that is localized to the skin on clinical assessment. Note that staging imaging is not required for the determination of eligibility, but if obtained prior to enrollment, all imaging must be consistent with localized cutaneous disease
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* Patients must not have received any prior chemotherapy, immunotherapy, targeted therapy, radiation, or surgical therapy for melanoma other than the permitted biopsy/excision of the lesion for which they are enrolling. Note that prior biopsies/surgery for other benign melanocytic lesions is permitted
Exclusion Criteria:
* Patients ≥ 18 years old with conventional adult-type melanoma are excluded. Note that patients 18-25 years old with atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasms are eligible
* Patients with clinical evidence of metastatic disease such as palpable malignant adenopathy or symptomatic distant metastases are not eligible
* Patients who have undergone re-excision to achieve a negative margin or sentinel lymph node biopsy for the melanocytic neoplasm under study are not eligible. Note that this does not exclude patients who have undergone the permitted diagnostic biopsy/excision, including re-biopsy, of the lesion
* Any of the following diagnoses
* Congenital nevi-associated proliferative nodules
* Agminated Spitz nevi/tumors
* Dysplastic nevus
* Combined nevus
* CRTC1::TRIM11 and/or MED15::ATF1 fused tumors (molecular testing is not required prior to enrollment)
* Pre-existing conditions:
* Solid organ transplant recipients
* Known melanoma predisposition syndrome (i.e., patients with previously known pathogenic variants in moderate and high penetrance melanoma susceptibility genes \[i.e., CDKN2A, CDK4, BAP1, POT1, TERT promoter, ACD, TERF2IP\] or Xeroderma Pigmentosum). Note germline testing is not required prior to enrollment
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
A First-in-human (FIH), Phase 1 Study of ML261, an Autologous Potency Enhanced Anti-DLL3 CAR T Cell Therapy, in Participants With R/R SCLC or Select NECs (SPECTRAL-1)
ML261 is an autologous DLL3-directed CAR T cell therapy being studied as first-in-human treatment in relapsed/refractory small cell lung cancer and select DLL3-expressing neuroendocrine carcinomas (including neuroendocrine prostate cancer) after prior systemic therapy.
NCT07488923 · Phase 1 · Moonlight Bio, Inc
Recruiting sites: Missouri, New Jersey, New York, Tennessee, Texas, Washington
Read full eligibility criteria
Inclusion Criteria
* ≥18 years of age at the time of signing the ICF
* Have been previously treated with at least one line of systemic standard of care (SOC) anti-cancer therapy for their respective cancer indication. Participants with locally advanced disease who are eligible for curative resection will be excluded.
* Have documented radiological disease progression/relapse during or after their most recent line of anti-cancer therapy with measurable disease on imaging, as assessed by RECIST v1.1
* Have histologically and/or cytologically confirmed diagnosis of select advanced or metastatic R/R solid tumor malignancy in one of the following: R/R SCLC, R/R GEP-NEC, R/R high-grade NEPC, R/R epNEC with biopsy-documented DLL3 expression on archival tissue or fresh biopsy by local or central assessment. CNS NEC is excluded. Participants with mixed histologies for any of these indications qualify if the small cell/neuroendocrine tumor cell percentage is \> 50%, except for high-grade NEPC where neuroendocrine component must be \> 20%.
* Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1
* Life expectancy ≥12 weeks
* Have adequate hematologic and end-organ function
Exclusion Criteria:
* Previous systemic anti-cancer therapies within the timeframes, as specified in the protocol.
* Prior exposure/treatment with DLL3-targeted CAR T therapy or any other genetically engineered adoptive T cell therapy.
* Prior allogeneic organ transplant (including allogeneic bone marrow transplant).
* Major surgical procedure within 4 weeks of the first dose of any study drug administration or anticipated to be in need of a major surgical procedure during the course of study.
* Participants with toxicities (as a result of prior anti-cancer therapy) which have not recovered to baseline or CTCAE v5.0 \<Grade 2, except for adverse events (AEs) not considered a likely safety risk: (e.g., alopecia, neuropathy, non-clinically relevant laboratory abnormalities).
* Symptomatic ascites or effusions (pleural or pericardial) requiring intermittent drainage.
* History of any other malignancy known to be active, with the exception of completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, ductal carcinoma in situ, early-stage prostate cancer that has been adequately treated, and other cancers from which the participant has been disease free for 3 years or longer or does not require treatment and in the opinion of investigator after discussion with the medical monitor are not likely to impact the patient's life expectancy.
* One or more of the following cardiac criteria: Unstable angina, Myocardial infarction within 6 months prior to Screening, New York Heart Association Class III to IV heart failure, clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block or third-degree heart block)
* Acute venous thromboembolism (VTE). VTEs without hemodynamic compromise, treated with stable doses of anticoagulants are allowed.
* Presence of clinically significant CNS pathology:
* seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, or cerebellar disease. History of these disorders requires discussion with the medical monitor.
* Presence of clinically active psychosis.
* Known brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the first dose of any study drug administration.
* Active systemic autoimmune disease or any other condition that requires, or is anticipated to require, systemic treatment with steroids or other systemic immunosuppressive agents, or participants who have received such agents within 4 weeks of leukapheresis and ML261 administration (further details provided in protocol body).
* Evidence of interstitial lung disease (such as idiopathic pulmonary fibrosis) or active pneumonitis of any etiology requiring treatment.
* Any active infection (defined as symptoms, signs, or radiographic) of bacterial, viral, or fungal or unknown etiology requiring systemic therapy within 14 days of leukapheresis. Participants with clinical and/or laboratory evidence of persistent infection will be excluded.
* Uncontrolled medical, psychological/psychiatric, or social condition that would interfere with the participant's participation or compromise the objectives of the study in the opinion of the Investigator and/or the Sponsor.
A Ph II Study of the TheraBionic P1 Device in Subjects With Hormone Positive Breast Cancer
The TheraBionic P1 device, which delivers self-administered amplitude-modulated electromagnetic fields (mechanism not further specified), is being studied as a treatment in patients with hormone receptor-positive, HER2-negative locally advanced/unresectable or metastatic breast cancer who have progressed on prior endocrine, CDK4/6 inhibitor, and chemotherapy/ADC therapies.
NCT07227831 · Phase N/A · Barbara Ann Karmanos Cancer Institute
Recruiting sites: Michigan
Read full eligibility criteria
Inclusion Criteria:
* Participant must have locally advanced/unresectable or metastatic Hormone Receptor (HR) positive, Human Epidermal growth factor receptor 2 (HER2) negative breast cancer as defined by the 2010 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (estrogen receptor \[ER\] and/or progesterone receptor \[PR\] \>1% and HER2 negative by immunohistochemistry \[IHC\] and/or fluorescent in situ hybridization \[FISH\]).
* Participant must have received and progressed on or are intolerant to all therapies known to confer overall survival benefit, including at least one line of endocrine + CDK4/6 inhibitor therapy AND one line of cytotoxic such as chemotherapy and/or antibody drug conjugates (ADCs).
* Participant must be a woman ≥ 22 years old and must be able to understand and sign an informed consent form.
* Participant must have a life expectancy of at least 3 months.
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
* it is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, women of childbearing potential must agree to avoid becoming pregnant starting at initiation of treatment up until at least 30 days after the last TheraBionic P1 session.
* Participants must meet one of the following:
* Surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
* Post-menopausal, defined as no menses for at least 12 months prior to the screening visit without alternative medical causation.
* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence methods such as calendar, ovulation, symptothermal, or post ovulation tracking are not acceptable.
* Not in a sexual relationship in which they may become pregnant (i.e. same-sex relationship)
* If they are of childbearing potential, agree to use at least one method of contraception. Withdrawal is not an acceptable contraceptive method.
Exclusion Criteria:
* Participants with known active secondary malignancy, unless, in the opinion of the investigator, it is unlikely to interfere with the safety and efficacy of the endpoints
* Participants that are taking any other investigational drugs.
* Participants that are pregnant or breastfeeding. If a breastfeeding participant would like to be part of this study, breastfeeding must be discontinued.
* Participants with active oral mucosal inflammation, ulceration, or other pathology that could interfere with the use of TheraBionic P1 device (for example: mucositis, thrush, bleeding mucosal lesions, oral herpes, aphthous stomatitis, mouth ulcers, chancre sores, gingivostomatitis, herpangina, aphthae).
* Participants receiving calcium channel blockers and any agent blocking L-type or T-type voltage gated calcium channels (for example: amlodipine, nifedipine, ethosuximide, ascorbic acid/vitamin C, etc.) unless their medical treatment is discontinued at least one day prior to treatment. Participant must agree to abstain from using calcium channel blockers for the duration of treatment on study.
* Participants that do not agree to be followed according to the study protocol or have cognitive or physical inability to use the device.
* Participants with a known severe (e.g., anaphylactic) allergy to nickel
A Phase II Study of Biomarker-Guided De-escalation Using Anthracycline-Free Neoadjuvant Chemoimmunotherapy in Early-Stage Triple Negative Breast Cancer (TNBC) Patients With High Tumor-Infiltrating Lymphocytes (TILs)
This trial studies biomarker-guided, anthracycline-free neoadjuvant chemoimmunotherapy (carboplatin plus paclitaxel chemotherapy combined with the PD-1 inhibitor pembrolizumab, with anthracycline added post-surgery only for those with residual disease) in early-stage (Stage II/IIIA-B) triple negative breast cancer with high tumor-infiltrating lymphocytes.
NCT07743190 · Phase 2 · Medical University of South Carolina
Recruiting sites: New York, South Carolina
Read full eligibility criteria
Inclusion Criteria:
Pre-Screening Phase:
1. Age ≥ 18 years at the time of informed consent.
2. Ability to understand and willingness to sign a written informed consent document in accordance with institutional and federal guidelines.
3. Histologically confirmed diagnosis of triple-negative breast cancer (TNBC) or hormone receptor-low invasive breast carcinoma, with clinical anatomic Stage II or Stage IIIA/B as defined by the AJCC 8th Edition Anatomic Breast Cancer Staging System.
a. Invasive tumor must be estrogen receptor (ER) and/or progesterone receptor (PR) negative or low, defined as ≤10% positive staining by immunohistochemistry (IHC).
b. HER2-negative disease, defined in accordance with current ASCO-CAP HER2 testing guidelines.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Screening and Treatment Phases:
General Eligibility
1. Individuals of childbearing potential must be willing and able to use highly effective contraception from the time of informed consent, throughout study treatment, and for at least 6 months after the last dose of trial therapy.
a. NOTE: Highly effective contraception is defined as methods with a failure rate \<1% per year when used consistently and correctly, and include: copper intrauterine device (IUD); bilateral tubal ligation/occlusion or other documented surgical sterilization; vasectomized partner with documented azoospermia, provided this is the sole sexual partner; or true sexual abstinence, defined as complete abstinence from heterosexual intercourse, when this is the participant's usual and preferred lifestyle. Use of hormonal contraceptive methods (including combined oral contraceptives, progestin-only pills, injectables, implants, hormonal IUDs, patches, or vaginal rings) is not permitted during the study and for at least 6 months after the last dose of study treatment.
2. Willingness and ability to comply with all study procedures, including scheduled visits, treatment plans, laboratory tests, and other protocol-specified requirements.
3. Willingness and ability to sign and date written informed consent prior to initiation of any study-specific procedures.
Disease Characteristics
4. Breast and axillary imaging (mammogram, ultrasound, or MRI) must have been completed within 45 days prior to registration.
5. Patients with abnormal axillary lymph nodes (identified clinically and/or radiographically) must undergo routine pathological confirmation via image-guided core biopsy or fine needle aspiration.
6. Presence of:
1. Measurable disease in the breast measuring at least 1cm with or without nodal involvement; or
2. Clinical T0 disease with biopsy-proven regional lymph node involvement (cT0N1-2M0), consistent with an overall anatomic stage II-IIIB classification.
i. For patients with clinical T0 disease confirmed by mammogram/US and MRI, nodal involvement must be documented by core needle biopsy or fine needle aspiration of an axillary or other regional lymph node demonstrating invasive breast carcinoma prior to initiation of neoadjuvant systemic therapy.
ii. Patients must not have undergone prior surgical excision of an invasive breast primary tumor that would account for the T0 designation (i.e., T0 must not be the result of complete prior excision of the primary breast lesion).
7. Patients with multifocal or multicentric disease are allowed if the dominant tumor is confirmed ER and/or PR ≤10%, and HER2-negative.
8. Patients with bilateral breast cancer are eligible if both tumors are HER2-negative.
9. Staging scans (e.g., CT chest/abdomen/pelvis with a nuclear bone scan) must be performed to rule out metastatic disease under any of the following conditions:
a. Two or more abnormal axillary lymph nodes on imaging, or b. Clinical suspicion of metastatic disease, or c. At the discretion of the treating physician.
Clinical and Laboratory Requirements
10. Peripheral neuropathy must be Grade ≤1 per CTCAE v5.0.
11. Complete history and physical examination performed within 45 days prior to registration.
12. Adequate hematologic and organ function as defined by the following:
a. Hematologic i. Hemoglobin ≥9.0 g/dL (without transfusion or erythropoietin support within 14 days prior to testing) ii. Leukocytes ≥3,000/μL iii. Absolute neutrophil count (ANC) ≥1,500/μL iv. Platelet count ≥100,000/μL b. Hepatic i. AST (SGOT) and ALT (SGPT) ≤3 × ULN ii. For participants without a history of Gilbert's syndrome, total bilirubin ≤1.5 × upper limit of normal (ULN) iii. For participants with a history of Gilbert's syndrome, total bilirubin ≤5 × ULN c. Renal i. Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 mL/min/1.73 m² by Cockcroft-Gault formula.
ii. Note: Patients with creatinine clearance 30-50 mL/min may be enrolled at the discretion of the Principal Investigator, given that paclitaxel is primarily hepatically metabolized and carboplatin dosing can be adjusted to renal function.
13. Cardiac function must be within acceptable limits, as follows: left ventricular ejection fraction (LVEF) ≥50% by
a. Echocardiogram (ECHO), or b. Multi-gated acquisition (MUGA) scan.
14. Participants with known human immunodeficiency virus (HIV)-infection must be on effective antiretroviral therapy (ART) at randomization and have an undetectable viral load test on the most recent test results obtained within six (6) months prior to randomization.
15. Participants with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within six (6) months prior to randomization, if indicated.
a. NOTE: No testing for HBV is required unless mandated by local health authority.
16. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have an undetectable HCV viral load test on the most recent test results obtained within six (6) months prior to randomization, if indicated.
1. NOTE: No testing for HCV is required unless mandated by local health authority.
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded from the study:
Pre-Screening Phase:
1\. Presence of tumor-infiltrating lymphocytes (TILs) \<30% based on central pathology review of hematoxylin and eosin (H\&E) stained slides.
Screening and Treatment Phases:
Disease-Related Exclusions
1. Presence of N3, inflammatory, or metastatic (M1) breast cancer.
2. History of other malignancies within the past 3 years, with the exception of:
1. Adequately treated non-melanoma skin cancer, or
2. Cervical carcinoma in situ, or
3. Other malignancies with a ≥3-year disease-free interval. Prior and Concurrent Therapy
3. Prior systemic therapy, radiation therapy, or definitive surgery for current breast cancer.
4. Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, or any other T-cell co-inhibitory or co-stimulatory agents.
5. Use of investigational agents or devices within 28 days prior to registration
6. Participant is planning to participate, currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Medical Conditions
7. History of severe (Grade ≥3) allergic reactions or hypersensitivity to study drugs or their components.
8. Uncontrolled diabetes mellitus or hypertension.
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy (7-day clearance period for immunosuppressant therapy prior to starting study treatment, if applicable).
10. History of solid organ transplant.
11. Active autoimmune disease requiring systemic treatment within the past 1 year.
12. Recent (within 12 weeks) or active non-infectious pneumonitis requiring corticosteroid therapy.
13. Major surgical procedure or active/severe infection within 14 days prior to registration.
14. Subject is a WOCBP who has had a positive pregnancy test within 24 hours prior to initiation of study treatment. Females will be determined to be not of child-bearing potential with a history of hysterectomy or with postmenopausal status of \>12 months.
15. Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 180 days after the last dose of trial treatment.
16. History of hypersensitivity to compounds that are similar to carboplatin and paclitaxel.
17. Has received major surgery and has not recovered adequately from the toxicity and/or complications before starting study treatment.
18. Has a history of non-infectious pneumonitis that required high-dose steroids and/or has current pneumonitis.
19. Has an active bacterial infection requiring systemic therapy.
20. Known psychiatric or substance abuse disorders that would interfere with the requirements of the trial.
Vaccination
21. Administration of live vaccines within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza or COVID vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
A Study of IDP-001 in Advanced or Metastatic Solid Tumors
IDP-001, a bispecific anti-EGFR/anti-CDCP1 antibody-drug conjugate carrying the microtubule-disrupting agent MMAE, is being studied as IV treatment in patients with advanced or metastatic squamous cell carcinomas (head and neck, cutaneous, cervical, esophageal, anal) and non-squamous NSCLC.
NCT07602842 · Phase 1/2 · InduPro, Inc.
Recruiting sites: California, Florida, Indiana, New York, Texas
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Histologically-confirmed advanced, metastatic, or recurrent solid tumors that is not amenable to surgical resection or other approved therapeutic options
* Satisfy requirements for prior treatments per tumor type as outlined in the protocol
* Measurable disease per RECIST v1.1
* Participant willing to provide tumor biopsies
* Adequate organ function
* Agree to contraception requirements as outlined in the protocol
* Life expectancy greater than 12 weeks
Exclusion Criteria:
* Any clinically significant cardiac disease
* Any clinically significant corneal disorder
* Known, active, and uncontrolled hepatitis B virus (HBV), hepatitis virus (HCV) or human immunodeficiency virus (HIV), or uncontrolled chronic or ongoing infectious requiring intravenous treatment.
* Active significant neurologic disorders
* Requires home oxygen
* Active autoimmune disease
* History or active skin disease requiring frequent treatment
* History of major immunologic reaction to prior immunoglobulin G-containing agent
* Clinically significant ascites or liver disease
* Uncontrolled diabetes or diabetic neuropathy
* Active bleeding disorders
* Participation in a concurrent clinical study in the treatment period
* Pregnant or lactating or planning to become pregnant
* Known hypersensitivity to IDP-001 or any of its ingredients
* Unresolved toxicities from previous anticancer therapy
* Has had a seizure prior to Screening
* Prior solid organ transplant or allogeneic stem cell transplant
* Current endocrinopathy
* History of Stevens-Johnson syndrome or Toxic Epidermal Necrolysis
* History or interstitial lung disease (ILD) or pneumonitis requiring treatment with systemic steroids
* Stroke or transient ischemic attack prior to Screening
* Participant has any other condition or illness that, in the opinion of the Investigator, may compromise participant safety, compliance, or interfere with the conduct and evaluation of the current study.
Note: Other inclusion and exclusion criteria may apply.
Adaptive Dosing of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma
This phase 2 trial studies an adaptive dosing regimen of nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4) immune checkpoint inhibitor combination therapy in patients with advanced/unresectable hepatocellular carcinoma not previously treated with anti-PD-1/L1 or anti-CTLA-4 agents.
NCT07689175 · Phase 2 · University of Texas Southwestern Medical Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC or combined HCC-cholangiocarcinoma will be excluded.
2. Patients may not have received any prior anti-PD-1/L1 or anti-CTLA-4 therapies for the treatment of advanced HCC.
3. Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
4. Child-Pugh Score B7-8
5. Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST v.1.1.
6. Prior locoregional therapy is allowed provided the target lesion has increased in size ≥25% since the cessation of locoregional therapy or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion.
7. Age ≥ 18 years.
8. ECOG performance score 0-2
9. Adequate organ and marrow function as defined below:
Platelet count ≥ 40,000/mm3
Hgb ≥ 8 g/dl
INR ≤ 2
AST, ALT ≤ 5 times ULN
Calculated creatinine clearance (CrCl) ≥ 35 mL/min. CrCl can be calculated using the Cockcroft-Gault method.
Albumin ≥ 2.0 g/dl
10. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
10a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
11\. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
1. Prior solid organ transplant.
2. Hypersensitivity to IV contrast; not suitable for pre-medication.
3. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
4. Active autoimmune disease that requires current systemic treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for conditions that, in the investigator's opinion, do not have a substantial hazardous risk such as asthma, and cutaneous and musculoskeletal rheumatologic conditions.
5. Known human immunodeficiency virus infection (testing not required) in a patient not on antiretroviral therapy and detectable viral load.
6. Prior malignancy that required systemic treatment within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Preneoplastic or malignant diagnoses that are indolent in nature and do not require active systemic treatment are not excluded.
7. If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if:
* Has evidence of progression by neurologic symptoms
* Has metastatic brain lesions that require immediate intervention.
* Has carcinomatous meningitis, regardless of clinical stability
8. Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
10. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
11. Prisoners or subjects who are involuntarily incarcerated.
12. Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion
This phase Ib/II trial evaluates the PRMT5 inhibitor BMS-986504 combined with the antifolate chemotherapy pemetrexed in patients with metastatic MTAP-deleted solid tumors (specifically pancreatic, biliary, esophageal, and colon cancers, plus other MTAP-deleted malignancies) who have progressed after at least one prior line of standard therapy.
NCT07594626 · Phase 1/2 · Northwestern University
Recruiting sites: Illinois
Read full eligibility criteria
Inclusion Criteria:
* COHORT A (INCLUDING SAFETY RUN IN, STAGE I AND STAGE II) AND COHORT B:
* Patients must have pathologically or cytologically confirmed metastatic solid tumor of gastrointestinal origin with MTAP deletion including pancreatic cancer, biliary cancer, esophageal cancer and colon cancer (Cohort A) or other metastatic solid malignancy with MTAP deletion (Cohort B) confirmed by validated next generation sequencing tissue techniques only
* NOTE: Both internal and external validated next generation sequencing (NGS) panels are acceptable
* Progressive disease (PD) after one previous standard of care line of treatment
* NOTE: symptoms from clinical evaluation for PD will be sufficient
* Patients must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, measured preferably by computed tomography (CT) scan
* Note: Tumor lesions in a previously irradiated area are not considered measurable unless they show unequivocal progression
* NOTE: There is no limit on previous treatment lines
* Patients who have received any neoadjuvant or systemic chemotherapy are eligible
* Note: treatment cannot have included prior pemetrexed unless in the case of non-small cell lung cancer (NSCLC) cancer type. Any prior intravesical therapy, or immunotherapy is allowed. At least 3 weeks (21 days) wash-out period from treatment since prior chemotherapy or radiation therapy or targeted agent is required
* Patients must be aged ≥ 18 years
* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (growth factor allowed and can be added at the discretion of the treating oncologist
* Growth factors are excluded from being used during the DLT observation period (cycle 1) unless they are being used to treat a grade 4 adverse event which will be counted as a DLT. If growth factors are being used for grade ≤ 3 toxicity, then patients will not be evaluable for DLT assessment
* Hemoglobin (Hgb) ≥ 8.5 g/dL (without the need for transfusion within the previous one week)
* Platelets (PLT) ≥ 100,000/mL (without the need for platelet transfusion within the previous one week)
* Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg/dL
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present
* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present
* Creatinine clearance ≥ 60 mL/min/1.73 m\^2 using the standard Cockcroft and Gault formula
* Patients must have the ability to comply with folic acid, vitamin B12 and steroids as directed by study team and as per standard of care for pemetrexed use
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Pemetrexed is known to be teratogenic. Reproductive toxicology studies with MRTX1719 have not been performed. The investigator or designee shall counsel patients of childbearing potential (POCBP) participants and male (as assigned at birth) participants who are sexually active with POCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant. If needed, participants should be advised to seek advice about egg or sperm donation and cryopreservation of germ cells before treatment
* Patients of childbearing potential POCBP
* A POCBP is any patient with an egg-producing reproductive tract who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy
* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
* POCBP are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional non-hormonal highly effective method of contraception. POCBP must agree to use a combination of a hormonal and a non-hormonal contraceptive method or a non-hormonal method alone that is highly effective (with a failure rate of \< 1% per year) during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
* POCBP participants must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period
* Male (as assigned at birth) participants will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with POCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male (as assigned at birth) participants should continue to use a condom during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
* POCBP partners of male (as assigned at birth) participants should be advised to use a highly effective method of contraception during the intervention period and for at least 6 months after the last dose of study intervention for the male participant, or according to approved local product label requirements for pemetrexed, whichever is longer
* Male (as assigned at birth) participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
* Male (as assigned at birth) participants must refrain from donating sperm during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
* Breastfeeding partners of male (as assigned at birth) participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms
* POCBP must have a negative pregnancy test prior to registration on study
* The ability to interrupt nonsteroidal antiinflammatory drugs (NSAIDS) or aspirin at higher dose (\> 1.3 g daily) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed
Exclusion Criteria:
* STAGE I AND II, COHORT A (INCLUDING SAFETY RUN IN) AND B:
* Patients who received prior pemetrexed containing chemotherapy (apart from NSCLC)
* Patients with prior treatment with a PRMT5 or MAT2A inhibitor therapy
* Patients with pre-existing clinically significant interstitial lung disease (ILD)
* Patients who have had chemotherapy or radiotherapy ≤ 21 days prior to planned treatment start date.
* Note: seven days or fewer of palliative radiotherapy for non-CNS disease, is permitted. No wash-out is required
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia and neuropathy per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
* Patients who are receiving any other investigational agents or devices. Patients start of study treatment will be based on their discontinuation and recovery from clinically significant adverse events from their most recent therapy or intervention prior to study enrollment
* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed
* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:
* Ongoing or active infection requiring systemic treatment
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification
* Note: To be eligible for this trial, patients should be class 2B or better
* Patients with presence of third space fluid which cannot be controlled by drainage
* Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy
* Patients who are not able to understand and voluntarily sign a written informed consent and is not willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
* Patients who are pregnant or nursing
* Patients with history of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications
* Patients with Fridericia's formula-corrected QT interval (QTcF) prolongation \> 480 msec, except for right bundle branch block, per the investigator's assessment
* Patients with ongoing need for a medication with a known risk of Torsade's de Pointes that cannot be switched to an alternative treatment prior to study entry
* Patients with ongoing need for a medication known as a strong inhibitor or strong inducer of cytochrome P450 3A4 (CYP3A4) and/or P-glycoprotein (P-gp) or a proton-pump inhibitor and potassium-competitive acid blockers that cannot be switched to an alternative treatment prior to study entry
* NOTE: The following drug interaction databases and other literature can be utilized to determine the CYP3A4/P-gp inhibitors and inducers
* Note: Please consult with the manufacturer for any uncertainties regarding potential CYP3A4 and P-gp modulators
* Patients with inability to comply with restrictions and prohibited treatments
* Patients taking any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 4 weeks prior to treatment. The concurrent use of any botanical preparation is not permitted while on study
* Patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it has been completed previously as part of the patient's health care, it should be documented for eligibility
* Patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Please note this lab is not a requirement for eligibility; however if it has been completed previously as part of the patient's health care, it should be documented for eligibility
* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with a known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Please note this lab is not a requirement for eligibility; however if it has been completed previously as part of the patient's health care, it should be documented for eligibility
* Patients who take live/attenuated vaccine received within 30 days of first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction
* Patient has not received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug:
* Surgery with general anesthesia - within 7 days of first dose of study drug
* Surgery with local anesthesia - with 3 days of first dose of study drug
Hotspot Stereotactic Ablative Radiotherapy Versus Traditional Stereotactic Ablative Radiotherapy for the Treatment of Early-Stage Non-Small Cell Lung Cancer
This trial compares hotspot-dosed stereotactic body radiation therapy (SBRT) versus standard SBRT for definitive treatment of early-stage (T1-3N0, Stage I-II) non-small cell lung cancer.
NCT07718672 · Phase 2 · Roswell Park Cancer Institute
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
* Age ≥ 18 years
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Diagnosed with T1-3N0 biopsy-proven NSCLC of the lung. Multiple primary lung tumors are allowed; however, each lesion requires histologic confirmation
* Metachronous lung tumors as defined as a new lung lesion in the setting of a historically treated lung cancer are allowed under certain conditions. The previous lung cancer must have been treated greater than 6 months prior to protocol therapy and this cancer must be considered controlled
* Eligible for SABR
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria:
* Patients with a history of a prior lung cancer will be excluded only if the previous treatment is within 6 months of the protocol therapy
* Mixed small cell and non-small cell lung cancer
* History of allogeneic organ transplantation
* History of primary immunodeficiency
* Patients must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment
* Active autoimmune disease that has required systemic treatment in the last 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Known EGFR or ALK mutation
* Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
* Pregnant or nursing female participant
* Unwilling or unable to follow protocol requirements
Measuring Circulating Tumor Deoxyribonucleic Acid Tumor Fraction to Guide Early 177Lu-PSMA-617 Treatment Discontinuation in Patients With Metastatic Castration-Resistant Prostate Cancer, DYNAMO Trial
This trial administers 177Lu-PSMA-617 (a PSMA-targeted radioligand therapy) or docetaxel chemotherapy to patients with metastatic castration-resistant prostate cancer, using ctDNA tumor fraction measurements to guide early treatment discontinuation.
NCT07698535 · Phase 2 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Willing and able to provide informed consent
* Adult males ≥ 18 years age
* History of histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine or small cell differentiation. If histology is not available, patients must have metastatic disease typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes)
* Evidence of metastatic disease on bone scan or CT scan
* Patient must have evidence of castration- resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e., ≤ 50 mg/dL)
* Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Prior treatment and progression on at least one androgen receptor pathway inhibitor (ARPI), in either castration-sensitive or castration-resistant setting
* Eligible for treatment with either 177Lu-PSMA-617 or docetaxel as per their respective Food and Drug Administration (FDA) labels
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Hemoglobin ≥ 9 g/dL
* Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft-Gault formula)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN. For patients with known Gilbert's Syndrome they must be ≤ 3 x ULN
* Able to comply with study requirements including provision of peripheral blood samples at specified time points for correlative studies
Exclusion Criteria:
* Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or provision of informed consent to participate in this study
* Evidence of metastatic neuroendocrine/small cell prostate cancer (NEPC). Note: baseline biopsy is not required
* Patients receiving any systemic therapy (aside from a luteinizing hormone-releasing hormone \[LHRH\] analogue) or radiotherapy within 2 weeks prior to study treatment
* Persistent toxicities (CTCAE grade \> 2) from prior cancer therapy, excluding alopecia and stable neuropathy
* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or active, uncontrolled infection. Examples include, but are not limited to uncontrolled seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
* Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count \< 200
* Patients with known active hepatitis (i.e. hepatitis B or C). Prior hepatitis C infection is allowed as long as polymerase chain reaction (PCR) is negative
* Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
* Serious cardiac disorder, including but not limited to uncontrolled ventricular arrhythmia, recent (within 12 months) myocardial infarction, resting electrocardiogram (ECG) indicating Fridericia's corrected QT interval prolongation \> 500ms, or congenital long QT syndrome
* Prior systemic chemotherapy with taxane chemotherapy, including in hormone sensitive setting (e.g. docetaxel or cabazitaxel)
* Brain metastases or active epidural disease (treated epidural disease is permitted)
* Note: baseline brain imaging is not required
* Contraindication to prednisone therapy including poorly controlled diabetes mellitus
Phase I/IIa Dose Finding Study of Triplet Regimen of Relatlimab Ipilimumab and NIvolumab in First Line Therapy of Metastatic Melanoma (TRINITY)
This trial evaluates a triplet combination of the immune checkpoint inhibitors relatlimab, ipilimumab, and nivolumab as first-line therapy in patients with unresectable stage III or metastatic (stage IV) melanoma.
NCT06683755 · Phase 1/2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥ 18 years old.
2. ECOG performance status 0-1
3. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
4. Histologically confirmed unresectable stage III or stage IV malignant melanoma (Stage IV).
5. At least one measurable target lesion according to RECIST 1.1. (Appendix 1), which previously was not treated.
• Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable
6. Tumor tissue from an unresectable or metastatic site of disease must be available for biomarker analyses. The biopsy should be a core biopsy, a punch biopsy, an excisional biopsy, or a surgical specimen. Fine needle aspiration is unacceptable for submission
* For Phase I participants: Pretreatment tissue must be available through either an archival sample obtained within at most 6 months and submitted as an FFPE tissue block or 30 unstained tumor tissue slides or a fresh pretreatment biopsy. Subsequent tumor biopsies will be optional.
* For Phase IIa participants: Either an archival sample submitted as an FFPE tissue block or unstained tumor tissue slides or a fresh pretreatment biopsy from safely biopsiable lesion. Note that if the patient has archival tissue available from a biopsy within 90 days of C1D1 and there has been no systemic treatment since that time then that tissue can be used in place of a fresh pre-treatment biopsy. Patients must also agree to undergo post treatment, cycle 2, tumor biopsies for research purposes. Subsequent biopsies will be optional.
7. No prior systemic lines of treatment for metastatic melanoma. Prior adjuvant or neo-adjuvant therapy will be permitted as long as it did not contain ipilimumab and the last dose has been \>6 months.
8. Prior radiation is allowed with a two week wash out period prior to initiation of treatment.
9. Adequate organ function as described below.
Table 2. Evaluation of Organ Function Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.5 X 109/L Platelets ≥ 100 X 109/L (≥ 60 for HCC) Hemoglobin ≥ 8.0 g/dL Renal Creatinine OR ≤1.5 × ULN OR Measured or calculatedb creatinine clearance ≥40 mL/min for participant with creatinine levels \>1.5 × institutional (GFR can also be used in place of creatinine or ULN CRCl) Hepatic
* 1.5 ×ULN OR direct bilirubin ≤ULN Total bilirubin for participants with total bilirubin levels AST (SGOT) and ALT (SGPT) ≤3.0 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR ≤1.5 × ULN unless participant is receiving prothrombin time (PTT) anticoagulant therapy as long as PT or Activated partial thromboplastin time aPTT wi withing therapeutic range of intended use of anticoagulants (aPTT) ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
b Creatinine clearance (CrCl) should be calculated per institutional standard. NOTE: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
10. Women of child-bearing potential (WOCBP) must not be breastfeeding and must have a negative pregnancy test within 3 days prior to initiation of dosing. She must agree to use an acceptable method of birth control from the time of the negative pregnancy test, through the duration of treatment with the study combination plus 5 half-lives of study treatment for a total of 5 months post -treatment completion. WOCBP must agree to adhere to the contraceptive guidance in Appendix 4. NOTE: A female participant is eligible to participate if she is not a woman of childbearing potential as defined Appendix 4.
11. All associated toxicity from previous or concurrent cancer therapy must be resolved (to ≤ grade 1 or baseline) prior to study treatment administration. This excludes low grade or non-serious toxicities. However, stable endocrinopathies requiring replacement therapy will be allowed.
12. Steroids for physiological replacement are allowed as long as it does not exceed 10 mg/day prednisone equivalents.
13. Participants must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period. BRAF V600 results need not be available at the time of study start.
14. Participants with asymptomatic brain metastases are eligible. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 10 days prior to study treatment administration. Patients with brain metastases treated with SRS will be allowed, as long as last radiation therapy is \>1 week.
Exclusion Criteria:
1. Patients with ocular melanoma.
2. Patients with symptomatic CNS metastases and/or requiring corticosteroid treatment.
3. History of known leptomeningeal involvement (lumbar puncture not required).
4. Patients who experienced Grade 3/4 immune-related adverse events with checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures (e.g. hypothyroidism)
5. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
6. Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
7. Subject has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
a. Skin Cancer Exclusion: Please note that basal cell carcinoma and squamous cell carcinoma is exempt from needing resection prior to treatment. (Resection can be completed after the start of treatment).
8. History of hepatitis B or hepatitis C infection, defined as reactive hepatitis B surface antigen (HBsAg) or detectable hepatitis C virus (HCV) RNA by qualitative testing. Patients with reactive HBsAg are excluded unless HBV DNA is \<500 IU/mL and the patient is receiving antiviral therapy.
a. NOTE: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care.
9. History of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
10. The use of corticosteroids is not allowed for 14 days prior to initiation of therapy (based upon 5 times the expected half-life of dexamethasone) except patients who are taking steroids for physiological replacement or in the case of Inhaled or topical steroids or other immunosuppressive medications. If alternative corticosteroid therapy has been used, consultation with the PI is required to determine the washout period prior to initiating study treatment.
11. Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study.
12. Non-healing wound, ulcer, or bone fracture.
13. Women who are breast-feeding or pregnant.
14. Uncontrolled intercurrent illness (i.e., active infection ≥ grade 2) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the subject's ability to participate.
15. History of clinically significant cardiac disease or congestive heart failure \> New York Heart Association (NYHA) class 2. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months or a history of myocarditis. Also, • prior myocarditis of any etiology. • Left ventricular ejection fraction (LVEF) assessment with documented LVEF \< 50% by either transthoracic echocardiogram (TTE) or multigated acquisition scan (TTE preferred test) within 6 months prior to the start of study treatment.
16. Troponin T (TnT) or I (TnI) \> 2 × institutional ULN. Participants with TnT or TnI levels between \> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 ULN. If TnT or TnI levels are between \>1 to 2 × ULN within 24 hours, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 × ULN, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. Notification of the decision to enroll the participant following cardiologist recommendation has to be made to the principal investigator.
17. Investigational drug use within 14 days (or 5 half-lives, whichever is shorter) of the first dose of the triplet therapy.
18. The use of herbal supplements within 7 days.
19. History of non-infectious pneumonitis that required steroids or current pneumonitis.
Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial]
This trial studies regorafenib (oral) combined with lorigerlimab (IV), whose mechanisms of action are not stated in the registry, as treatment for high-risk colorectal cancer patients with molecular (ctDNA-detected) residual disease after completion of definitive/adjuvant therapy.
NCT07071961 · Phase 2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Eligibility Criteria
* Histological confirmation of CRC
* Post-R0 resection of stages II, III, or IV CRC and all planned adjuvant therapies have been completed.
* No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay
* Evident MRD as defined by positive ctDNA assay. Participants may be identified for enrollment with any Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA assay for MRD. MRD status will be confirmed with the Signatera assay prior to initiation of therapy (unless the prior testing was also done with Signatera in which case this test would not require confirmation)
* Adequate organ and marrow function as defined below:
* Absolute neutrophil count: ≥1,000/mcL
* Platelets: ≥100,000/mcL
* Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowed if Gilbert's syndrome is documented.
* AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN (≤5 x ULN for participants with liver involvement of their cancer).
* Creatinine clearance ≥40 mL/min. Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation as follows: Clcr (mL/min) = \[(140 - age) x (weight in kg) ÷ \[72 x (serum creatinine in mg/dL)\] \[0.85 if female\]
* ECOG performance status (PS) of 0 or 1
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of regorafenib in these participants, children \<18 years of age are excluded from this study.
* Able to understand and is willing to sign a written informed consent document.
* The effects of RELO on the developing human fetus are unknown. For this reason and because regorafenib appears to be teratogenic in animal models, women of child-bearing potential (refer to MDA Policy CLN 1114) must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation and for at least 4 months after the last dose. This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
O Postmenopausal (no menses in greater than or equal to 12 consecutives months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal
* range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.) Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice, however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of administration
Exclusion Criteria
* Concurrent treatment with drug with which the interactions are considered clinically significant by investigator (as outlined in section 0). Major surgical procedure or significant traumatic injury within 21 days before start of study medication. Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Grade 2 or higher peripheral neuropathy per CTCAE v5.0.
* Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment except for participants who may be receiving low dose prednisone (specifically receiving ≤10 mg prednisone or equivalent within 7 days of treatment initiation).
* Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
* Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation.
* Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant).
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. The study will allow replacement therapy with thyroxine, insulin or physiologic corticosteroid replacement therapy for autoimmune conditions that are well-controlled.
* Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCICTCAE v5.0), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.
* Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>II), myocarditis, or serious cardiac arrhythmia.
* Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.
* Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2 per CTCAE v5.0.
* Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted). Patient should refrain to receive live-virus vaccines for 120 days following the last dose of lorigerlimab.
* Evidence of any serious bacterial, viral (active HIV, HCV or HBV), parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug.
* Subject is pregnant or breast feeding or planning to become pregnant while enrolled in the study, up to the final EOT visit.
* History of (non-infectious) pneumonitis that required steroids, ongoing pneumonitis, or history of interstitial lung disease.
* History of GI perforation or GI bleeding within 4 weeks, significant diverticulitis or flare within 4 weeks, and acute pancreatitis within 4 weeks.
* Grade \> 3 (per CTCAE v5.0) proteinuria (\> 3.5 g/24 hours)
* Grade \> 3 (per CTCAE v5.0) hypertension (systolic blood pressure \> 160 or diastolic blood pressure \> 100).
* Evidence or history of bleeding diathesis or coagulopathy within 6 months of start of treatment. Subjects with clinically significant thrombotic, embolic, venous, orarterial events, deep vein thrombosis or pulmonary embolism within 6 months of start of treatment. Participants with incidental findings that have started anticoagulation and are stable are allowed.
* Ongoing infection \> Grade 2 NCI-CTCAE v5.0.
* Symptomatic metastatic brain or meningeal tumors.
* Presence of a non-healing wound, non-healing ulcer, or bone fracture.
* Major surgical procedure or significant traumatic injury within 28 days before start of study medication
* Renal failure requiring hemodialysis or peritoneal dialysis.
SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer
This trial studies SX-682, an oral CXCR1/2 inhibitor, combined with atezolizumab, a PD-L1-targeting monoclonal antibody, in patients with advanced/metastatic or recurrent NSCLC who have progressed after prior platinum doublet chemotherapy and anti-PD-1/PD-L1 therapy.
NCT07322341 · Phase 2 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Age 18 years and older
* Ability to understand and willingness to sign a written informed consent document
* Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK fusion, ROS1 fusion or RET fusions.
* For participants with NSCLC harboring an oncogenic alteration other than the above must have received prior targeted therapy (e.g. small molecule inhibitor therapy or antibody drug conjugates). A wash-out of at least 5 half-lives is required prior to start of study treatment
* Metastatic or recurrent NSCLC. Stage 3C per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment
* Participants must have received and progressed on at least 6 weeks of treatment with prior anti-PD-1 or anti-PD-L1 therapy for advanced disease. Also, participants must have received prior platinum doublet chemotherapy. Anti-PD1/PD-L1 therapy may have been received concurrently with chemotherapy or as sequential therapy (e.g. anti-PD1 followed by chemotherapy).
* For participants who received neoadjuvant, adjuvant and/or consolidation anti-PD-1 or anti-PD-L1 therapy for stage 1 - 3 NSCLC: If they experienced disease progression ≤ 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy, this counts as the allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease.
* For participants who experienced disease progression more than 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy for advanced disease, this is not considered anti-PD-1 or anti-PD-L1 therapy for advanced disease. These patients must have received anti-PD-1 or anti-PD-L1 therapy for stage 4 or recurrent disease
* Participants must have a minimum of 28 days after the last dose, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy prior to initiation of study treatment, including investigational agents
* Participants must have at least one site of measurable disease as determined by the investigator, using RECIST v 1.1 criteria documented within 28 days prior to study treatment initiation
* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at the time of informed consent and at the time of treatment initiation
* Participants must be willing to provide pre-treatment archived specimen (taken within a year of trial entry) or undergo a biopsy procedure if archived specimen is not available.
* If biopsy is not deemed safe, it may be waived after discussion with principal investigator (PI)
* Participants must be willing to provide an on-treatment biopsy, to be obtained at 6 - 9 weeks, if deemed safe by the treating physician
* Platelet count \> 100,000/μL
* Absolute neutrophil count \> 1,500/μL
* Hemoglobin \> 9.0 g/dL. Participants may be transfused to meet this criterion
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \< 2.5 times upper limit of normal
* Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease: serum bilirubin ≥ 3 x ULN
* Creatinine clearance ≥ 30 mL/min
* For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
* Participants of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal methods must be supplemented by barrier method) prior to treatment initiation, during treatment, and for 5 months after the last dose of atezolizumab
* Negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to initiation of study treatment for participants of childbearing potential. Pregnant or breast-feeding women or intention of becoming pregnant during study treatment or within 5 months of last dose of atezolizumab are not eligible
Exclusion Criteria:
* Presence of other active cancers within the last 2 years. Participants with another cancer who have received definitive therapy at least 2 years previously and no evidence of recurrence are eligible. All participants with previously treated in situ carcinoma are eligible, as are participants with history of non-melanoma skin cancer
* Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no ongoing requirement for steroids within 7 days prior to start of study treatment, no history of intracranial hemorrhage or spinal cord hemorrhage. If the patient is receiving anti-convulsant therapy, the dose is considered stable
* Participants with untreated CNS metastases may be enrolled as long as they meet the above criteria. Participants with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment
* Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment
* Participants must not have an active autoimmune disease that has required immune modulating treatment within 1 year prior to consenting (i.e., disease modifying agents, long term corticosteroids). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed. Short-term steroid therapy (≤ 2 weeks) is allowed
* Inability to discontinue corticosteroid therapy; steroids must be tapered off 7 days prior to first dose of SX-682. Limited steroid use for allergic reactions is acceptable
* Known history of primary immunodeficiency
* History of organ transplant or prior allogenic stem cell transplantation that requires use of immunosuppressives
* Current symptomatic pneumonitis and any past history of immune checkpoint inhibitor related pneumonitis regardless of steroid treatment history
* Prior history of grade 3 or higher immune checkpoint inhibitor (ICI)-induced immune-related adverse event (AE) (immune related adverse event \[irAE\]) except endocrine irAEs that are resolved or managed with replacement therapy
* Radiotherapy within 7 days of start of study treatment
* Major surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment.
* Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed
* Electrocardiogram (ECG) demonstrating a Fridericia's corrected QT interval (QTcF) interval \> 480 msec or patients with congenital long QT syndrome
* Severe lung disease (e.g. chronic obstructive pulmonary disease \[COPD\]) who cannot stop steroids 7 days prior to start of study treatment
* Serious cerebrovascular and cardiac disease defined as:
* Active unstable angina pectoris
* Congestive heart failure New York Heart Association (NYHA) \> grade 3
* Acute myocardial infarction within 3 months of consenting
* Stroke or transient ischemic attack within 3 months of consenting
* Known active chronic infections: Active hepatitis B, hepatitis C and tuberculosis. Testing is not required for assessment of eligibility per investigator judgment. Active infection requiring IV antibiotics within 7 days of study treatment initiation.
* Hepatitis C virus (HCV) infection: Patients with known history of HCV infection are eligible if HCV viral load is below the limit of quantification per local assay per investigator judgment.
* Hepatitis B virus (HBV) infection: Patients with known history of HBV infection are eligible if HBV viral load is below the limit of quantification and negative hepatitis B surface antigen (HBsAg) per local assay per investigator judgment
* Known uncontrolled HIV (human immunodeficiency virus) infection
* Participants with known HIV infection are allowed if they are receiving anti-retroviral therapy, have CD4+ T-cell count \> 350 cells/µL within 6 months prior to study treatment initiation and no history of AIDS- defining opportunistic infection
* Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
* History of leptomeningeal disease
* Treatment with investigational therapy within 28 days prior to initiation of study treatment, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
* Known allergy or hypersensitivity to any component of the atezolizumab formulation
Study of NXP900 With Lorlatinib in ALK+ Lung Cancer
Phase 1b study of NXP900, an oral SRC family kinase inhibitor, combined with the ALK kinase inhibitor lorlatinib in patients with advanced ALK-positive non-small cell lung cancer previously treated with lorlatinib.
NCT07784959 · Phase 1 · Nuvectis Pharma, Inc.
Recruiting sites: Virginia
Read full eligibility criteria
Inclusion Criteria:
* 18 years old or older
* Unresectable, metastatic or locally advanced ALK-positive NSCLC.
* Must have received lorlatinib as first or second line TKI
* One prior line of systemic chemotherapy is permitted
* Must have tolerated the dose level of lorlatinib actively being explored in the study or a higher dose
Exclusion Criteria:
* Known single or compound ALK domain mutations that cause resistance to lorlatinib, or known actionable oncogenic driver alterations other than ALK with approved targeted therapies available, such as, MET or EGFR mutations or HER2 overexpression
* Any contraindications to treatment with lorlatinib according to the lorlatinib United States Prescribing Information (USPI)
Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors
[177Lu]Lu-DWJ155 is a radioligand therapy (paired with [68Ga]Ga-DWJ155 for imaging) whose specific molecular target is not stated in the registry, studied in patients with advanced, previously treated HER2+/HR+/HER2-low or triple-negative breast cancer, NSCLC, gastric/GEJ cancer, and bladder cancer.
NCT07660055 · Phase 1 · Novartis Pharmaceuticals
Recruiting sites: Nebraska
Read full eligibility criteria
Inclusion Criteria:
* Male or female patients age ≥ 18 years.
* Patients with one of the following histologically or cytologically confirmed and documented malignancies who have progressed on or been intolerant to standard of care therapy, and are not considered appropriate for any standard therapy with proven benefit, in the investigator's judgment:
* Dose Escalation:
* Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
* Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
* Advanced NSCLC without actionable genetic alterations (AGAs) with disease progression after prior therapy in the advanced setting
* Advanced NSCLC with AGAs who have received prior treatment
* Measurable disease as determined by RECIST version 1.1.
* Dose Expansion:
* Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
* Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
* Advanced HR+/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
* Advanced HR-/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
* Advanced HR-/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
* Advanced NSCLC with AGAs, who have received prior treatment
* Advanced NSCLC without known AGAs who have received prior treatment.
* Advanced gastric/GEJ cancer with HER2 IHC 3+ or 2+ (ISH + or -), following disease progression after prior therapy in the advanced setting
* Advanced bladder cancer following disease progression after prior therapy in the advanced setting
* Measurable disease as determined by RECIST version 1.1.
Exclusion Criteria:
* Out-of-range laboratory values defined as:
* Creatinine clearance \< 60 mL/min (calculated using CKD-EPI 2021 formula, or measured)
* Total bilirubin \> 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin \>3.0 x ULN) or direct bilirubin \> 1.5 x ULN
* Alanine aminotransferase (ALT) \> 3 x ULN, except for patients with tumor involvement of the liver who are excluded if ALT \> 5 x ULN
* Aspartate aminotransferase (AST) \> 3 x ULN, except for patients with tumor involvement of the liver who are excluded if AST \> 5 x ULN
* Lipase \> 1.5 x ULN
* Absolute neutrophil count (ANC) \< 1.5 x 109/L
* Hemoglobin \< 9 g/dL
* Platelet count \< 100 x 109/L
* Initiation of hematopoietic colony stimulating factors, thrombopoietin mimetics, or erythroid stimulating agents initiated ≤ 2 weeks prior to imaging agent administration.
* Use of transfusion support ≤4 weeks prior to imaging agent administration.
* Impaired cardiac function or clinically significant cardiac disease.
* Unmanageable urinary tract obstruction or urinary incontinence.
* Any serious uncontrolled infection (acute or chronic).
* Pregnant or breastfeeding women.
* Treatment with any of the following anti-cancer therapies prior to imaging agent administration within the stated timeframes:
* Prior treatment with any therapeutic radiopharmaceutical
* \< 10 half-lives for any imaging radiopharmaceutical
* ≤ 4 weeks for external beam radiation therapy (EBRT) or brachytherapy
* ≤ 6 months for lung-directed external beam radiotherapy
* Patients with non-tumor uptake of \[68Ga\]Ga-DWJ155 in tissues or organs that, in the opinion of the investigator, increases the risk associated with \[177Lu\]Lu-DWJ155 treatment.
Other protocol-defined inclusion/exclusion criteria may apply.
Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400
ABBV-400 is an investigational agent (mechanism/target not specified in the registry) given IV as monotherapy or combined with itraconazole or bevacizumab, studied in a Phase 1 basket trial of advanced/metastatic solid tumors including hepatocellular carcinoma, pancreatic ductal adenocarcinoma, biliary tract cancer, esophageal squamous cell carcinoma, triple-negative or HR+/HER2- breast cancer, head and neck squamous cell carcinoma, and platinum-resistant ovarian/peritoneal/fallopian tube cancer.
NCT06084481 · Phase 1 · AbbVie
Recruiting sites: California, Colorado, Florida, Illinois, Michigan, Missouri, New York, North Carolina, Ohio, Rhode Island, South Carolina, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Laboratory values meeting the criteria laid out in the protocol.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Documented diagnosis of locally advanced or metastatic hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), squamous cell carcinoma of the esophagus, (ESCC), triple negative breast cancer (TNBC), hormone receptor+/HER2-breast cancer (HR+/HER2-BC), head and neck squamous-cell-carcinoma (HNSCC), or Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer (by World Health Organization \[WHO\] criteria). Participant meets the criteria for disease activity laid out in the protocol.
Exclusion Criteria:
* Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-400. Palliative radiation therapy for bone, skin, or subcutaneous metastases with 10 fractions or less is permitted and not subject to a washout period.
* Unresolved clinically significant AEs \> Grade 1 from prior anticancer therapy.
* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis, including but not limited to those listed in the protocol.
* History of clinically significant, intercurrent lung-specific illnesses, including those laid out in the protocol.
* Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). Participants may continue on antiepileptic therapy if required.
* History of other active malignancy, with the exception of those laid out in the protocol.
* Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), and prior pneumonectomy.
TLR9 Immunotherapy for Peritoneal Carcinomatosis
ACM-CpG, a TLR9 immunotherapy agent, is administered via intraperitoneal injection in a Phase 1 dose-escalation study for inoperable peritoneal carcinomatosis or malignant ascites from colorectal or appendiceal adenocarcinoma.
NCT07658196 · Phase 1 · Brown University
Recruiting sites: Rhode Island
Read full eligibility criteria
Inclusion Criteria:
* Patients eligible for inclusion in this study must meet all of the following criteria:
1. Male or female patients age ≥ 18 years of age at the time of informed consent
2. Must be able to provide written informed consent, stating an understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements
3. Must have documented CRC or appendiceal adenocarcinoma peritoneal carcinomatosis or malignant ascites. Primary tumor may be intact and limited liver and/or lung disease is permitted
4. Must have evaluable disease by physical examination, serum tumor markers, radiologic assessment, or laparoscopic visual assessment
5. Must have a life expectancy of ≥ 12 weeks as estimated by the investigator
6. Must have an ECOG status of ≤ 2
7. Patients with acceptable laboratory values defined as:
* Estimated creatinine clearance (calculated using Cockcroft-Gault formula, or measured) ≥ 60 mL/min, not dialysis dependent
* Total bilirubin ≤ 1.5 mg/dl, unless elevated bilirubin is clearly related to Gilbert syndrome (and total bilirubin \< 6.0 mg/dl)
* Alanine aminotransferase (ALT) ≤ 3.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) ≤ 3.5 x ULN
* Absolute neutrophil count \> 1.0 x 109/L (must be independent of blood product administration)
* Platelet count \> 100 x 109/L (must be independent of blood product administration)
* Hemoglobin ≥ 8 g/dL (must be independent of blood product administration)
8. Surgically sterile patients or patients of childbearing potential (CBP) who agree to use highly effective methods of contraception during study dosing and for 6 months after last dose of study drug
9. All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to administration of study drug
Exclusion Criteria:
1. Has received prior TLR9 therapy
2. Has received chemotherapy, radiotherapy, or biological cancer therapy within 21 days or 5 half-lives (whichever is shorter) of the start of treatment
3. Has received an investigational agent within 28 days of the start of treatment
4. Has received a commercial vaccine (flu, COVID, etc.) within 2 weeks of C1D1
5. Has any unresolved toxicity ≥ Grade 2 from previous anti-cancer therapy, except for stable chronic toxicities (≤ Grade 3) that are not expected to resolve
6. Has a history of histologically confirmed metastases outside of the peritoneal cavity, liver, or lungs
7. Has high volume liver or lung metastases, defined as \> 50% replacement of the liver volume by metastatic disease or \> 5 lung lesions greater than 1 cm in size
8. Tumor causing biliary obstruction not amenable to stenting or percutaneous drainage
9. Ongoing or untreated intra-abdominal infection or bowel obstruction
10. Has known, clinically active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) (Note: Testing is not required)
11. Receiving continuous systemic corticosteroid therapy (≥ 10 mg/day of prednisolone or equivalent)
12. Clinically significant cardiac disease or impaired cardiac function, including any of the following:
* A history of newly diagnosed transmural myocardial infarction, cerebral infarction, or pulmonary embolism within 6 months, except those approved by the medical monitor
* A history of newly diagnosed deep vein thrombosis (DVT) within 3 months
* Left ventricular ejection fraction (LVEF) \< 50%
* QTc \>480 msec
13. Active bacterial, viral, or fungal infection: patients with ongoing use of prophylactic antibiotics, antiviral agents, or antifungal agents remain eligible as long as there is no evidence of active infection
14. Other active malignancy within 2 years excluding cutaneous squamous or basal cell carcinomas
15. Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
16. History of hypersensitivity to TLR9 agonists
17. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation)
Phase 3 Trial of Tarlatamab (SC vs IV) in Extensive-Stage Small Cell Lung Cancer After Platinum Based First-line Chemotherapy (ES-SCLC)
This trial compares subcutaneous versus intravenous administration of tarlatamab, a DLL3xCD3 bispecific T-cell engager, in relapsed extensive-stage small cell lung cancer after prior platinum-based chemotherapy.
NCT07778316 · Phase 3 · Amgen
Recruiting sites: Florida, Michigan, Nebraska
Read full eligibility criteria
Inclusion Criteria:
* Participant has provided informed consent prior to initiation of any study specific activities/procedures.
* Age ≥ 18 years (or legal adult age within country, whichever is older) at the time of signing the informed consent.
* Histologically or cytologically confirmed SCLC with demonstrated progression or relapse.
* Participants who progressed or recurred following 1 platinum-based regimen.
* Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
* Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
* Minimum life expectancy of 12 weeks.
* Adequate organ function.
* History of central nervous system (CNS) metastases are allowed with considerations defined in the protocol.
Exclusion Criteria:
Disease Related
\- Any previous diagnosis of non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation that has transformed to SCLC, or mixed SCLC and NSCLC histology, with exceptions defined in the protocol.
Other Medical Conditions
* Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 6 months prior to first dose of study treatment.
* History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
* Current evidence or history of non-infectious pneumonitis/ILD (interstitial lung disease) that required steroids or other immunosuppressive treatment.
* History of other malignancy within the past 2 years, with exceptions defined in the protocol.
* Presence or history of viral infection based on criteria per protocol.
* History of solid organ transplantation.
* Symptoms and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection requiring antibiotics within 7 days prior to the first dose study treatment.
* Known sensitivity or a contraindication to any of the products or components.
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
Prior/Concomitant Therapy
* Prior systemic anticancer therapy within 30 days of enrolment
* Prior history of severe or life-threatening events from any immune-mediated therapy.
* Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment.
* Live and live-attenuated vaccines within 28 days prior to the start of study treatment.
* Receiving another anticancer therapy for a malignancy other than SCLC.
* More than 1 prior line of anticancer therapy for SCLC.
* Participation in a tarlatamab clinical trial or prior therapy with any selective inhibitor of the delta-like ligand 3 (DLL3) pathway.
* Treatment in an alternative investigational trial within 28 days prior to enrolment.
* History of allergy or hypersensitivity to similar products (eg, drugs with a similar chemical structure or other monoclonal antibody) or any excipient.
Other Exclusions
* Participants unable to have SC injections administered in the abdomen or thigh.
* Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements.
* History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.
Stereotactic MR-Adaptive Radiation Therapy for Early-stage Renal Cancer
MRI-guided stereotactic body radiation therapy (single-fraction 26Gy, MRgRT via MR linac with adaptive planning and respiratory gating) is being studied as definitive treatment for early-stage (cT1a-b, N0, M0) primary renal cell carcinoma in patients who are inoperable or decline surgery/ablation.
NCT07767500 · Phase N/A · NYU Langone Health
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
1. Patients at or over 18 years old.
2. Patients may enter the study if they are diagnosed with bilateral kidney cancer, recurrent kidney cancer, or if they have previous or current history of a another primary cancer, given all other inclusion criteria met.
3. Have a pathologically confirmed diagnosis of renal cell carcinoma (RCC) of any histology, or radiographic diagnosis if biopsy is not clinically indicated, consistent with standard clinical practice where imaging findings provide sufficient diagnostic certainty. In such cases, biopsy may not be required to avoid additional procedural risk; however, inclusion of patients without histologic confirmation may introduce some diagnostic uncertainty, which will be considered in the interpretation of study results.
4. Patients must be deemed a suboptimal surgical or ablation candidate, as determined by the patient's primary urologist at NYU Langone Health and confirmed by multidisciplinary consensus, or may be individuals who decline surgery or ablation following appropriate clinical evaluation and discussion..
o At or before the time of enrollment, a note documenting multidisciplinary consensus supporting active treatment will be recorded in the patient's chart.
5. Tumor stage of cT1a-b, cN0, M0 (i.e. less than 7 cm in greatest dimension).
6. Be technically and anatomically appropriate for MRI-guided radiation therapy, as determined by patient's primary radiation oncologist.
o Factors considered will include distance between tumor and bowel, tumor movement with respiration as assessed by 4-dimensional (4D) imaging, and prior radiotherapy in close proximity to treatment which would lead to high dose overlap from the prior radiation fields.
7. Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Have life expectancy of 2 years or more.
Exclusion Criteria:
1. An MRI contraindication (e.g. severe claustrophobia or MRI-incompatible device). In the event of mild claustrophobia, patients will be permitted to take anti-anxiety medication as required for simulation and treatment.
2. A pre-treatment estimated glomerular filtration rate \< 30 cc/min.
3. Visceral, nodal, or bony metastatic disease.
4. Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit.
5. Pregnant or breastfeeding individuals, or individuals of childbearing potential who have a positive pregnancy test at screening or prior to radiation treatment initiation.
6. Individuals of childbearing potential who are unwilling to use one highly effective method of contraception and one additional effective method of contraception, or abstain from heterosexual intercourse, during study participation and for 6 months after completion of study therapy.
7. Previous high dose radiation treatment to an overlapping area.
8. Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
9. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
10. Is on systemic therapy that is reasonably expected to modify radiation sensitivity and cannot be stopped for a sufficient washout period to allow for radiation treatment.
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
VMD-102, an oral small-molecule selective PKC epsilon kinase inhibitor, is being studied as monotherapy for dose-finding and preliminary efficacy in advanced/metastatic hepatocellular carcinoma, uveal melanoma, renal cell carcinoma, non-small cell lung cancer, and colorectal cancer that have failed or are unsuitable for standard of care.
NCT07636785 · Phase 1/2 · VM Discovery, Inc.
Recruiting sites: Arizona
Read full eligibility criteria
Inclusion Criteria:
* Histological or cytological or radiological diagnosis of advanced (unresectable and/or metastatic) HCC, MUM, RCC, NSCLC and CRC that is not responsive to standard of care (SOC), had progressed following SOC, is intolerant to SOC, or for whom the SOC is not considered appropriate by the investigator.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0, or 1.
* Has at least one measurable target lesion according to RECIST v1.1 \[Response Evaluation Criteria In Solid Tumors\], or mRECIST \[modified RECIST\] for unresectable HCC participants, and either (a). has not been previously treated with local therapy (e.g., radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy), or (b). if the target lesion was within the field of local therapy, the lesion has shown an increase in size of 25% or greater following local therapy.
* Adequate organ function evidenced by:
Hematology
* Hemoglobin ≥ 9 g/dL (SI Units: 90 g/L) (post-transfusion if transfusion-dependent)
* Platelet count ≥ 60000/mm3 (60 x109/L) without support(transfusion) within 7 days of testing
* Absolute neutrophil count (ANC) ≥ 1500/mm3 (1.5x109/L) Chemistry
* Total bilirubin (TBIL) ≤ 2.0 x upper limit of normal (ULN). (For participants with Gilbert's syndrome, TBIL ≤3.0 x ULN provided that direct bilirubin DBIL) is \<30% of the TBIL)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 1 ≤ 5 x U LN (participants with advanced HCC or liver metastases)
* AST and/or ALT 1 ≤ 3 x ULN (participants without known liver disease or liver metastases)
* Calculated creatinine clearance or 24h urine creatinine clearance ≥50 mL/min using Cockroft-Gault formula.
* Serum creatinine ≤ 1.5x ULN
Coagulation (unless taking an anti-coagulant):
* Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (except for participants receiving therapeutic anticoagulants)
* International normalized ratio (INR) ≤ 1.5 unless the participant is receiving anticoagulant therapy as long as the participant is within therapeutic range of intended use of anticoagulants
* Albumin ≥2.8g/d/L.
* For HCC participants: the diagnosis must be made based on American Association for the Study of Liver Diseases (AASLD) Guidelines with confirmed advanced (unresectable) HCC staged by Barcelona Clinic Liver cancer criteria (BCLC). Cirrhosis will be staged by Child-Pugh score, and such a score ≤ 6 will be eligible for Phase 1 and ≤7 for Phase 2.
* Participants must either have available archival tumor tissue samples, or consent to fresh tumor tissue sampling prior to the first dose unless the biopsy is not safe or not feasible per investigator assessment and with medical monitor approval.
* Women of childbearing potential (WOCBP) must have a negative pregnancy test prior to enrolment and agree to use a highly effective and acceptable method of contraception from the time of informed consent (or screening) until 6 months after the last dose of investigational agent.
* Male participants who are sexually active with a female partner of childbearing potential must agree to use a condom with spermicide from first dose of investigational agent until 6 months after the last dose, and refrain from sperm donation during that period. Abstinence from heterosexual intercourse is an acceptable method only if the participant's usual lifestyle already includes abstinence.
* Participant has a life expectancy of ≥3 months.
* No history of liver transplantation.
* Ability to swallow and absorb an orally self-administered medication in tablet form.
* Have completed any prior chemotherapy, monoclonal antibody or immunotherapy (e.g., tumor vaccine, cytokine, or growth factor given to control the cancer) at least 4 weeks or 5 half-lives (whichever is shorter) before study drug administration. Exceptions to these prior therapy timeframes are possible, on a case by case basis, following discussion and mutual agreement between Investigator and Sponsor.
* Adverse effects related to prior anticancer therapies must have either returned to baseline or resolved to Grade 0 or 1. Some toxicities with higher grades such as alopecia, immunotherapy-induced hypothyroidism or adrenal insufficiency or panhypopituitarism requiring stable doses of hormone replacement therapy or rash from prior therapy may be permitted with medical monitor approval.
Exclusion Criteria:
* Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or tumor embolization within the past 2 weeks or 5 half-lives (whichever is longer).
* Currently pregnant, nursing, or planning to become pregnant during the course of study.
* The Fridericia Corrected QT (QTcF) interval ≥ 480 msec.
* Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Section 14.8); or presence of clinically significant and uncontrolled cardiac disease, as assessed by the investigator. Such as but not limited to: symptomatic congestive heart failure, unstable angina, cardiac arrhythmia.
* Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the participant's safety or interfere with assessment of the drug.
* Psychological, familial, sociological, geographical or other concurrent conditions that would interfere with safety evaluation, limit the participant's ability to follow the procedures in the protocol or otherwise jeopardize compliance with the protocol. Participants with uncontrolled major depression, bipolar disorder, or severe anxiety disorder are excluded.
* Participants have multiple factors that affect their oral medication (such as inability to swallow and intestinal obstruction or resection).
* Participants have long-term unhealed wounds or fractures.
* Participants have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.
* Any current medical conditions, including impairment of GI function or GI disease, which would alter the absorption, distribution, metabolism or excretion of VMD-102 including but not limited to:
* Severe uncontrolled nausea or vomiting.
* Severe uncontrolled diarrhea or ongoing active diarrhea requires medications (e.g. bile acid sequestrant, loperamide).
* A history of short bowel syndrome; irritable bowel syndrome with diarrheal signs/symptoms or require medications.
* Clinically diagnosed malabsorption secondary to bowel resection.
* Active Ulcerative colitis or Crohn's disease requiring medication for control.
* Surgical procedures of the GI tract impacting the drug absorption such as but not limited to small bowel resection and gastric bypass.
* Unstable central nervous system (CNS) metastases. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least one cycle prior to the first dose and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are on stable doses of steroids for at least one cycle prior to the first dose.
* Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC or HCC due to cirrhosis caused from autoimmune-associated hepatitis.
* Hepatitis B surface antigen (HBsAg) positive with detectable the hepatitis B virus load (HBV DNA) \>100 IU/mL. Participants on active HBV therapy with viral loads \<100 IU/mL should stay on the same therapy throughout study intervention and at least 12 weeks after the study is over. Participants cannot be actively co-infected with hepatitis C virus (HCV; HCV RNA detectable) or hepatitis delta virus (HDV; HDV RNA detectable).
* Positive HBsAg, with or without detectable HBV DNA, if there is evidence in the medical history of an advanced stage of cirrhosis ( Child-Pugh B) or history of decompensated chronic liver disease
* HCV antibody (HCVAb) positive and HCV viral load (HCV RNA) detectable. Previous HCVAb positive with HCV RNA undetectable due to treatment (DAAs or interferon) is allowed but the treated participants must have completed their treatment at least 12 weeks prior to starting study intervention and HCV RNA must be documented at below the limit of quantification.
* History of allogeneic tissue/organ transplantation (including bone marrow, stem cell, liver, or kidney transplants), except those that do not require immunosuppressive therapy (e.g., corneal or hair transplants).
* Coronavirus disease 2019 (COVID-19) or any live attenuated vaccine within 4 weeks of study entry.
* Participants with active alcohol and/or substances abuse, Phosphatidylethanol (Peth) must be \<50 ng/mL).
* Concurrent secondary malignancy other than that being treated in this study. Exceptions to this exclusion include malignancies treated curatively and have not recurred within 2 years prior to study entry or tumors treated with curative intent that have expected cure rates of \>90% such as but not limited to: basal cell and squamous skin cancer and completely resected carcinoma in situs.
* Participants have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage. Exception may be possible, on a case by case basis, e.g. if no more than one paracentesis in a month and a drain is pre-placed for the participant to drain, following discussion and mutual agreement between Investigator and Sponsor
* Participants have long-term unhealed wounds or fractures.
* Participants receiving known potent P-glycoprotein (P-gp) efflux transporter inhibitors that cannot be discontinued 3 days prior to the start of study treatment and during the course of the Phase 1 study.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drug, or excipients.
* Known history of uncontrolled human immunodeficiency virus (HIV) infection.
* Any other condition that, in the opinion of the Investigator or the medical monitor, could increase the risk to the participant, interfere with study participation, or affect the proper interpretation of study results and objectives. Such conditions may include but are not limited to, active infections, uncontrolled diabetes, psychiatric illness, social situations, and concomitant therapies.
A Phase I Study of SIM0505 in Participants With Advanced Solid Tumors
SIM0505 is an investigational drug whose mechanism of action is not stated in the registry, being tested as monotherapy in a phase 1 dose-escalation/optimization study for adults with advanced/metastatic solid tumors including platinum-resistant ovarian, fallopian tube, primary peritoneal, uterine serous, renal cell (clear cell/papillary), and NSCLC who have progressed on prior standard therapy.
NCT06792552 · Phase 1 · NextCure, Inc.
Recruiting sites: Florida, Georgia, Louisiana, Massachusetts, New Jersey, New York, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria:
1. Written informed consent is obtained prior to any procedures that are not considered standard of care.
2. ≥18 years of age.
3. In Part 1:
1. Participants with histologically or cytologically confirmed advanced solid tumors, who have failed or are ineligible for standard of care therapies.
2. Have progressed on at least one prior systematic anti-tumor regimen, and presence of at least one evaluable lesion according to RECIST Version 1.1. Measurable lesions are required in the backfill period.
3. In the backfill period, eligible tumor types are limited to high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, USC, clear cell RCC, papillary RCC and adenocarcinoma of NSCLC without actionable mutation of epidermal growth factor receptor (EGFR). For participants with NSCLC, presence of CDH6 expression through immunohistochemical examination of tumor tissue by central laboratory is required.
4. In Part 2: Participants must have a diagnosis of specific type of metastatic or locally advanced solid tumors and have progressed on or cannot benefit from the most recent systematic anti-tumor regimen (unless otherwise specified), with presence of at least one measurable lesion according to RECIST Version 1.1.
Platinum-resistant ovarian cancer cohort:
1. Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
2. Have platinum-resistant disease, defined as: participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a best response of CR or PR, and then progressed between \>90 days and ≤180 days after the date of the last dose of platinum; participants who have received ≥2 lines of platinum therapy must have progressed ≤180 days after the date of the last dose of platinum.
3. At least one line of therapy containing anti-VEGF therapy (e.g., bevacizumab or suvemcitug or their biosimilar), unless the participant is not eligible for treatment with anti- angiogenic treatment due to precautions/intolerance. Has had prior poly-ADP ribose polymerase (PARP) inhibitors for subjects with documented breast cancer gene (BRCA) mutation (germline and/or somatic), unless the subject is not eligible for treatment with a PARP inhibitor. Has had prior treatment with mirvetuximab soravtansine for participants with documented high folate receptor alpha expression, unless the subject is not eligible for treatment with mirvetuximab soravtansine due to precautions/intolerance, or if the treatment is not approved or available locally. In the PROC cohort, topoisomerase inhibitor payload ADC-pretreated participants should have received at least one prior topoisomerase inhibitor payload ADC.
Renal cell carcinoma cohort:
1. Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.
2. For clear cell RCC: Participants who have progressed on or after systemic treatment including a programmed cell death protein 1 or programmed death ligand 1 (PD-1/PD-L1) checkpoint inhibitor and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI), either given concurrently or in separate lines of therapy.
3. For papillary RCC: Participants without any prior systemic treatment is acceptable.
Uterine serous carcinoma cohort:
1. Participants with histologically- or cytologically-confirmed USC.
2. Have progressed on or after systemic treatment that contained platinum-based chemotherapy.
Non-Small Cell Lung Cancer cohort:
1. Participants with histologically- or cytologically-confirmed adenocarcinoma of NSCLC without actionable mutation of EGFR.
2. Presence of CDH6 expression through immunohistochemical examination of tumor tissue.
3. For participants without actionable mutations: Have progressed on or after systemic treatment including anti-PD-1/PD-L1 antibody and platinum-based chemotherapy, either given concurrently or in separate lines of therapy. Progression within 6 months after completion of adjuvant therapy is considered failure of first-line therapy.
4. For participants with actionable mutations other than EGFR: Have failed at least one established standard anti-cancer targeted therapy, anti-PD-1/PD-L1 antibody and platinum-based chemotherapy (PD-1/PD-L1 and chemotherapy either given concurrently or in separate lines of therapy) or in the opinion of the Investigator have been considered ineligible for a particular form of standard of care therapy on medical grounds.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Life expectancy of ≥12 weeks.
7. Have adequate organ function as indicated by the laboratory values listed within the protocol.
8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study treatment. WOCBP or male participants who have sexual relations with WOCBP are required to use highly effective contraceptive methods, and agree to refrain from donating sperm/egg from signing of informed consent through 180 days after the last dose of study treatment.
9. Able to provide tumor tissue sample (archival or newly obtained core or excisional biopsy). For Part 1: At biomarker-screening (for NSCLC) or screening (for non-NSCLC) visit of a tumor lesion not previously irradiated for CDH6 testing.
For Part 2: Willing to undergo fresh tumor biopsy at biomarker-screening visit (for NSCLC) and screening visit (non-NSCLC) from a lesion that can be biopsied at an acceptable clinical risk as judged by the investigator.
Exclusion Criteria:
1. For Part 2: has clear cell, mucinous or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer; mixed nonsmall cell and small cell carcinoma, or adenosquamous cell lung cancer with an adenocarcinoma component \<50% (the participant is eligible if the adenocarcinoma component is ≥50%).
2. For Part 2: Participants with primary platinum refractory ovarian cancer, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy.
3. Any other malignancy within 2 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence.
4. Known untreated CNS metastases and/or leptomeningeal metastases. Participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment). In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to the first dose of study treatment. Imaging performed within 28 days prior to the first dose of study treatment must document radiographic stability of CNS lesions and be performed after completion of any CNS-directed therapy.
5. History of bowel obstruction within 3 months prior to the first dose of study treatment.
6. Known psychiatric disorder or drug abuse that would interfere the study requirements.
7. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
8. Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
9. History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.
10. Prior exposure to other CDH6-targeted agents.
11. Prior exposure to an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000) for all cohorts except for the topoisomerase inhibitor payload ADC-pretreated participants in PROC cohort.
12. Has not recovered (i.e., to CTCAE version 5.0 Grade 1 or to baseline) from previous anticancer therapy-induced AEs. Grade ≤2 AEs with no impact on participant safety are exceptions to this criterion and may qualify for the study.
13. Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of SIM0505.
14. Major surgery within 2 weeks of receiving the first dose of study treatment.
15. Has received prior anti-cancer therapies within the following time frames prior to the first dose of study treatment: previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks; anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study treatment; Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks; and/or radiation therapy within 2 weeks for focal radiation or within 4 weeks for wide-field radiation.
16. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
17. Administration of strong or moderate CYP3A4 inhibitors or drugs with known risk of Torsades de Pointes (TdP) ≤ 7 days or 3 half-lives (whichever is longer) prior to the first dose of SIM0505.
18. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
19. Active hepatitis B or hepatitis C infection.
20. Participants with clinically significant cardiovascular diseases.
21. History of allogeneic organ transplantation or graft-versus-host disease.
22. Known hypersensitivity to study drug or any of the excipients.
23. Participant is pregnant or breastfeeding.
24. Other conditions that researchers consider inappropriate for inclusion.
A Study Evaluating Adherence, Tolerability, and Patient Reported Outcomes of Giredestrant in Participants With ER+/HER2- Early Breast Cancer Who Are Intolerant to Adjuvant Aromatase Inhibitor Therapy (novERA Breast Cancer)
Giredestrant, an oral selective estrogen receptor degrader (SERD), is being studied as adjuvant endocrine therapy in patients with Stage I-III ER+/HER2- early breast cancer who are intolerant to prior adjuvant aromatase inhibitor therapy.
NCT07541079 · Phase 3 · Genentech, Inc.
Recruiting sites: California, District of Columbia, Michigan, Nevada, New Jersey, New York, Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
* Considered appropriate for treatment with endocrine therapy (ET)
* Histologically confirmed diagnosis of ER+/HER2-, Stage I-III (low-/medium-/high-risk) early breast cancer (eBC)
* Documented ER+ tumor according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP), defined as ≥1% of tumor cells stained positive
* Documented HER2- tumor according to ASCO/CAP
* Postmenopausal females at the time of signing the Informed Consent Form
* Documented use of a prior adjuvant aromatase inhibitor (AI) (i.e., anastrozole, exemestane, or letrozole) for a total of ≥6 months
* Documented use of an adjuvant AI (i.e., anastrozole, exemestane, or letrozole) for the consecutive ≥3 months immediately prior to consent
* Participant and investigator agree that current symptoms on AI are intolerable and warrant a switch in therapy to attempt sustained treatment
* Documented Grade 2 or 3 adverse events, per NCI CTCAE v6.0, determined by the investigator to be associated with AI therapy's intolerance
* Participant and investigator planning the first switch from an AI
* Has completed the following: (neo)adjuvant chemotherapy (if administered), definitive surgery of primary breast tumor(s) and/or axillary lymph nodes dissection (ALND) and/or sentinel lymph node biopsy (SLNB) and/or radiotherapy
* Eastern Cooperative Oncology Group Performance (ECOG) Performance Status 0 or 1
Exclusion Criteria:
* Participation within 6 months before enrollment in any other clinical study involving an investigational adjuvant treatment including anti-cancer agents
* Diagnosis of rheumatoid arthritis, psoriatic arthritis, or other inflammatory connective tissue disease
* Any prior fulvestrant or any oral selective estrogen receptor degraders (SERDs)
* Have active cardiac disease or history of cardiac dysfunction
* Have clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis (e.g., hepatitis B virus \[HBV\] or hepatitis C virus \[HCV\]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis
* Treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
* Have had any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study
A Study of Cyclophosphamide, Methotrexate, Fluorouracil (CMF) for People With Breast Cancer
This phase 2 trial evaluates feasibility of dose-dense adjuvant/neoadjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF), with paclitaxel also given, in breast cancer patients age 70 and older, including a triple-negative cohort previously treated with neoadjuvant carboplatin/paclitaxel +/- pembrolizumab.
NCT07768436 · Phase 2 · Memorial Sloan Kettering Cancer Center
Recruiting sites: New Jersey, New York
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically confirmed adenocarcinoma of the breast confirmed at MSK. The patient must have had diagnostic biopsy or completion of primary surgical management, within 3 months of enrollment. Results of HER-2/neu, estrogen receptor, and progesterone receptor are required for study entry.
* Patients must be ≥ 70 years of age.
* Patients must have ECOG performance status \>2 (Karnofsky score of ≥ 60%).
* Patients may have received hormonal therapy for the purpose of chemoprevention.
* Adjuvant/neoadjuvant chemotherapy decision to treat based on the discretion of investigator
* Cohort 1 only: Patients have any histology except Her 2 Neu positive in the adjuvant or neoadjuvant setting
* Cohort 2 only: Patients have triple negative (ER- (10%) PR-Her 2 Neu -) in the neoadjuvant setting
* Cohort 2 only: Patients have received at least 1 dose of carboplatin/paclitaxel +/- pembrolizumab in the neoadjuvant setting
Required Organ Function
Adequate hematologic function defined as follows:
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
* Platelets ≥ 100,000 cells/mm3
Adequate renal function defined as follows:
° Creatinine clearance (CrCL) of \>30 mL/min by the Cockcroft-Gault formula:
CrCl (mL/min) = \[(\[140 - age(years)\] x weight (kg))/72 x creatinine (mg/dL)\] (x 0.85 for female patients)
Adequate hepatic function defined as follows:
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* AST and ALT ≤3 x institutional ULN
* Patients or their Legally Authorized Representative must give written, informed consent indicating their understanding and willingness to participate in the study.
Exclusion Criteria:
* Stage IV breast cancer
* CARG score- high Frail 4 or more as assessed by CAIT
* Her 2 Neu positive 3+/amplified breast cancer
* No prior chemotherapy within 1 year of study enrollment
* Cohort 2 only: patients may not receive pembrolizumab during dd CMF treatment
AB801 in Combination With Chemotherapy and Immunotherapy for the Treatment of Patients With Borderline Resectable, Locally Advanced or Metastatic Cholangiocarcinoma or Pancreatic Cancer
AB801, an AXL-blocking agent, is being studied in combination with chemotherapy (gemcitabine/cisplatin/oxaliplatin/irinotecan/leucovorin/fluorouracil) and PD-1/PD-L1 immunotherapy (durvalumab or zimberelimab) in previously untreated, borderline resectable, locally advanced, or metastatic cholangiocarcinoma or pancreatic adenocarcinoma.
NCT07619313 · Phase 1 · Jonsson Comprehensive Cancer Center
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Male or female ≥ 18 years of age and willing and able to provide informed consent
* Previously untreated cytologically or histologically confirmed, at least one measurable lesion via Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of cholangiocarcinoma or pancreatic adenocarcinoma meeting following criteria:
* Cholangiocarcinoma
* Borderline resectable/locally advanced cholangiocarcinoma: to be defined as unresectable disease on evaluation by a hepatobiliary multi-disciplinary tumor board/surgeon based on tumor size/location, vascular involvement, and absence of extrahepatic metastasis.
* Metastatic cholangiocarcinoma: Patients with metastatic cholangiocarcinoma patient who have not received prior systemic therapy
* Pancreatic adenocarcinoma
* Borderline resectable pancreatic adenocarcinoma: There are multiple definitions of borderline resectable pancreatic ductal adenocarcinoma (PDAC). For the purposes of this study, borderline resectable disease will be identified per the National Comprehensive Cancer Network (NCCN) criteria. Per this definition, borderline resectable PDAC is defined as the presence of any one or more of the following on CT:
* An interface between the tumor and superior mesenteric artery (SMA) or celiac axis (CA) measuring \< 180º of the circumference of the vessel wall.
* An interface between the tumor with the common hepatic artery without extension into the celiac axis or hepatic artery bifurcation allowing for safe and complete resection and reconstruction.
* An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180° of the circumference of the vessel wall
* Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
* An interface between the primary tumor and the inferior vena cava (IVC)
* Locally advanced pancreatic adenocarcinoma: Multiple guidelines defining locally advanced PDAC have been developed. For the purposes of this study, locally advanced PDAC cases will be identified per the definition developed by the NCCN. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT:
* Interface between the tumor and SMA or CV measuring \> 180º of the circumference of the vessel wall or solid tumor contact with the CA and aortic involvement.
* Occlusion of the SMV-PV that is not amenable to resection and venous reconstruction
* Metastatic pancreatic adenocarcinoma: Patients with metastatic pancreatic adenocarcinoma who have not received prior systemic therapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Absolute neutrophil count (ANC) ≥ 1.5x10\^9/L
* Platelets ≥ 100x10\^9/L
* Hemoglobin ≥ 9 g/dL
* Creatinine clearance (Ccr) ≥ 50 mL/min (as calculated by Modified Cockcroft-Gault formula)
* Serum total bilirubin ≤ 2x upper limit of normal (ULN) or \< 3x ULN if Gilbert's syndrome
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 2.5 X ULN; \< 5x ULN in patients with liver metastases
* Women with no childbearing potential because of surgery or who are at least 1 year postmenopausal (ie, 12 months post last menstrual period) or with menopause confirmed by follicle-stimulating hormone testing, OR
* Women of childbearing potential (defined as any female who has experienced menarche and is not permanently sterile or post-menopausal) must use an effective nonhormonal method of contraception (intrauterine device or intrauterine system; condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; or vasectomized male partner if he is the sole partner of that participant) or practice true abstinence for the duration of the study and for up to 14 months after the last systemic treatment
* Male participants must use an effective method of contraception (condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; or vasectomy) or practice true abstinence as defined throughout the study and for up to 11 months after the systemic treatment
* Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted
* Products with known potential to prolong the corrected QT (QTc) interval should be avoided when possible. When able will replace non-prolonging QTc acting drug when available and if medically necessary
* Major surgery as defined by the Investigator must be completed at least 4 weeks before study treatment administration. Participants should have recovered from the surgical procedure prior to the first dose being administered
* Adequate baseline tumor tissue sample for correlative studies
Exclusion Criteria:
* Previous treatment with any of planned study drugs in cholangiocarcinoma, though patients with one cycle of gemcitabine/cisplatin/durvalumab will be considered eligible
* Previous treatment with any of planned study drugs in pancreatic adenocarcinoma, though patients with one cycle of FOLFIRINOX will be considered eligible
* Peripheral neuropathy \> grade 2
* Known status of HIV which is not well-controlled (CD4 \< 300) at the time of study eligibility. Patients with controlled and treated HIV/hepatitis C virus (HCV) and an undetectable viral load are allowed
* Untreated hepatitis B infection; Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection (testing is not mandatory, unless known active or known history of infection or required by local regulation):
* Participants with resolved or treated HCV (ie, HCV antibody positive but undetectable HCV ribonucleic acid \[RNA\]) will not be excluded from this study
* Underlying medical conditions that, in the Investigator's opinion, will make the administration of investigational product (IP)(s) hazardous, including but not limited to:
* Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis
* Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of the IP,
* Active infection or antibiotics within 48 hours prior to study screening;
* A condition or unresolved adverse event (AE) from a prior investigational drug that may obscure the interpretation of toxicity determination or AEs,
* History of prior solid-organ transplantation
* Any history of malignancy less than 5 years prior to the time of study eligibility (Patients with history of skin cancers excluding melanoma and cancers with a very low risk of recurrence i.e., low grade prostate cancer, thyroid cancer and low risk cervical cancer will be eligible for participation)
* Serious medical comorbidities such as New York Heart Association Class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
* Known family history or personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least grade 3 (QTc \> 500 ms)
* Screening 12-lead electrocardiogram (ECG), in triplicate, with a measurable QTc interval of \> 450ms
* Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a grade 2 or greater bleeding episode in the 3 weeks before day 1
* Known pregnancy, nursing women or positive pregnancy test. Requirement for women of childbearing potential (WOCBP): Negative serum pregnancy test at screening and serum or urine prior to dosing on cycle 1 day 1, within 24 hours prior to the start of treatment (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]). WOCBP must also have a negative serum or urine pregnancy test every 3 weeks, within 24 hours prior to the start of treatment
* Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the investigator
* History of trauma or major surgery within 28 days prior to the first dose of IP
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Any active or documented history of autoimmune disease, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment, except for the following:
* Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger.
* Endocrinopathies where the participant is stable on hormone replacement therapy
* History of Hashimoto syndrome within 3 years of the first of study treatment that resolved to hypothyroidism alone
Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
This phase III trial compares radiation (IMRT) plus cetuximab (an EGFR-targeting monoclonal antibody) versus radiation plus carboplatin/paclitaxel chemotherapy as primary treatment for previously untreated, locoregionally advanced head and neck squamous cell carcinoma (larynx, hypopharynx, oropharynx, or oral cavity) in patients unable to receive cisplatin.
NCT07441681 · Phase 3 · NRG Oncology
Recruiting sites: California, Delaware, Florida, Illinois, Iowa, Kansas, Kentucky, Missouri, New York, Ohio, Pennsylvania, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
* Local evaluation of p16 status is required for all oropharynx patients prior to registration
* Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
* Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
* Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB
* Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
* AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
* AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
* p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years
* Eligible p16-Positive Oropharyngeal Primaries
* AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: \> 10
* AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: \> 10
* AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
* Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
* The following are required prior to registration:
* Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
* Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
* Age ≥ 18
* Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
* Patients must have a contraindication to cisplatin as defined in the following bullet points:
* Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
* Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
* Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* History of hearing loss, defined as either:
* Existing need of a hearing aid OR
* ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
* age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
* Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
* HNCIG omega score \< 0.80
* (Modified) Charlson Comorbidity Index (CCI) ≥ 1
* G-8 score ≤ 14
* Not pregnant and not nursing
* Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
* No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior surgery for the study cancer
Comparison of Proton or Intensity Modulated Radiation Therapy After Surgery for Endometrial or Cervical Cancer
This trial compares postoperative proton radiation therapy versus intensity modulated radiation therapy (IMRT) delivered to the pelvis after hysterectomy in patients with cervical or endometrial carcinoma.
NCT04567771 · Phase N/A · Mayo Clinic
Recruiting sites: Arizona, Florida, Minnesota
Read full eligibility criteria
Inclusion Criteria:
* Histologically confirmed diagnosis of cervical or endometrial cancer
* Must have undergone an open or robotic hysterectomy (total abdominal, vaginal, radical, or total laparoscopic) for carcinoma of the cervix or endometrium
* History and physical prior to registration
* Documentation of history of:
* Smoking status
* Pelvic infection
* Pelvic inflammatory disease
* Endometriosis
* Planned to receive either proton or IMRT radiation treatment, with use of rectal balloon, at any Mayo Clinic site
* Plan for RT to pelvis with or without para-aortic lymph node irradiation
* If received high-dose chemotherapy prior to registration, last dose must have been given \>= 21 days prior to start of RT
* Complete blood count (CBC) performed within 21 days prior to registration
* Computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, or PET/MRI for staging before registration; may be pre-operative (op) or post-op
* Eastern Cooperative Oncology Group (ECOG) performance score 0-2
* Provide written informed consent
* Willing to complete quality of life (QOL) questionnaires
Exclusion Criteria:
* Receiving external beam boost dose during RT
* Distant metastases
* Gross disease at time of RT
* Histology of endometrial stromal sarcoma, leiomyosarcoma, melanoma or small cell carcinomas
* Patients who exceed the weight/size limits of the treatment table
* Positive or close surgical margins (=\< 3 mm)
* Prior RT to the pelvis
* Planned to receive inguinal node RT
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be immunosuppressive.
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
* Severe, active co-morbidity defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
* Transmural myocardial infarction within the last 6 months
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
* Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
* Patients unwilling to have rectal balloon placed on a daily basis during RT
Imlunestrant and Abemaciclib for the Treatment of Estrogen Receptor Positive Breast Cancer in Patients With Minimal Residual Disease, MIRI Trial
Imlunestrant (an oral estrogen-lowering agent) plus abemaciclib (an oral enzyme/cell-growth inhibitor) are studied as adjuvant therapy in patients with localized ER-positive, HER2-negative stage I-III breast cancer who have minimal residual disease (detectable ctDNA) after prior treatment.
NCT07191717 · Phase 2 · Jonsson Comprehensive Cancer Center
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Participants must have localized ER+ (≥ 10% on surgical pathology), HER2 negative, any grade, invasive breast cancer. Pathological stage (from time of surgery, including patients who received neoadjuvant therapy) I - III by American Joint Committee on Cancer (AJCC) 8th edition staging
* Note: Invasive breast cancer must be ER+ in ≥ 10% of the cells and HER2 negative (immunohistochemistry \[IHC\] 0 or 1+ and/or fluorescence in situ hybridization \[FISH\] negative with a ratio \< 2) by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. For Immunohistochemistry (IHC) 2+, the tumor must be FISH negative with a ratio \< 2. ER, progesterone receptor (PR) and HER2 measurements should be performed according to institutional (local) guidelines, in a Clinical Laboratory Improvement Act (CLIA)-approved setting
* Detectable ctDNA in a CLIA-certified lab (separate pre-screening consent available) within the past six months. Participants must have no clinical or radiographic evidence of recurrence as determined by the treating investigator
* Confirmation of adequate archival tissue (either initial biopsy or surgical specimen) (15-20 unstained slides cut at 5 µm or 1 block) required before study entry. If adequate surgical tissue is available, this is preferred. Otherwise tissue from diagnostic biopsy is acceptable. If adequate tissue not available, principal investigator (PI) approval is required prior to study entry
* No prior history of other malignancies within past 5 years (besides breast cancer as per inclusion #1). Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin. No concurrent malignancy or other serious medical condition as deemed by the investigator
* Participants may or may not have received (neo)adjuvant chemotherapy and/or biological therapy at the time of screening, with no more than grade 1 residual toxicity (except ≤ grade 2 neuropathy or ≤ grade 2 alopecia)
* Participants may or may not have received adjuvant radiotherapy, with no more than grade 1 residual toxicity
* Pre- and postmenopausal women and men are eligible. Premenopausal women must have a negative serum pregnancy test at time of screening
* Pregnancy testing does not need to be pursued in female patients who are:
* Age ≥ 60 years; OR
* Age \< 60 with intact uterus AND amenorrhea for 12 consecutive months or more AND estrogen (estradiol) levels within postmenopausal range
* OR status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation
* Must be ≥ 18 years of age
* History of CDK 4/6 inhibitor is permitted provided the last dose was more than 6 months ago (from consent date)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky ≥ 70%)
* Patients must currently be on endocrine therapy in the adjuvant setting and must have received (neo) adjuvant endocrine therapy for at least 24 months (cumulative duration)
* Ability to understand and the willingness to sign a written informed consent document. Patient must sign the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements
* Participants must currently be receiving adjuvant endocrine therapy and have been on adjuvant endocrine therapy for at least 2 years. Adjuvant endocrine therapy can be either tamoxifen or aromatase inhibitor (AI), i.e prior use of any AI, including letrozole, anastrozole or exemestane, or tamoxifen is allowed. Concurrent gonadotrophin releasing hormone (GNRH) agonist is required with AI in pre - and/or peri-menopausal patients and men
* Absolute neutrophil count ≥ 1.5 × 10\^9/L
* Platelets ≥ 100 × 10\^9/L
* Hemoglobin ≥ 9.0 g/dL
* Serum creatinine \< 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x institutional upper limit of normal (ULN)
* Total bilirubin \< institutional 1.5 times ULN; or total bilirubin ≤ 3.0 x institutional ULN. Patients with Gilbert's Syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted
* The patient is able to swallow oral medications
Exclusion Criteria:
* Participants with metastatic disease (including contralateral axillary lymph nodes) or inflammatory breast cancer. Of note, if a patient had locally advanced breast cancer leading to inflammation, this would not exclude the patient on the grounds of inflammatory carcinoma
* Participants who have had CDK 4/6 inhibitor therapy within the past 6 months. Use of prior CDK 4/6 inhibitor with last dose more than 6 months ago is permitted
* Participants who are receiving any other anti-cancer investigational agents. Participation in other observational studies is permitted
* History of other malignancies within past 5 years, except ductal carcinoma in situ of the breast, cervical cancer in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin. No concurrent malignancy or other serious medical condition as deemed by the investigator
* Herbal products and supplements will generally not be allowed, but specific supplements (such as cannabidiol \[CBD\] oil) can be considered on a case-by-case basis by Overall PI
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (e.g. estimated creatinine clearance \< 30ml/min), unstable angina pectoris, cardiac arrhythmia, a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, stomach resection, or small bowel resection) are ineligible. Patient with active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]). Screening for HIV and hepatitis is not required for enrollment
* The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
* A history of venous thromboembolism (VTE): deep vein thrombus or pulmonary embolism. An exception can be made for patients with a history of an uncomplicated venous catheter-related occlusion. The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
* History of hypersensitivity to imlunestrant, abemaciclib or any of the components in either medication
* HIV-positive participants not on antiretroviral therapy are at increased risk of lethal infections when treated with marrow-suppressive therapy and should not be enrolled until their HIV is managed. If the HIV is well controlled, participants may participate in this study
* Pregnant women are excluded from this study because embryo-fetal toxicity is a potential side effect of abemaciclib and imlunestrant. For this reason, women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception prior to study entry, for the duration of treatment, and for at least 3 months after the completion of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential. All WOCBP must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of the investigational agent(s). Registration may occur prior to this pregnancy test. If the pregnancy test is positive, the patient must not receive protocol treatment and must not continue in the study. WOCBP is defined as follows:
* Any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or a bilateral oophorectomy) OR
* Any female who is not postmenopausal defined as:
* Age ≥ 60 years; OR
* Age \< 60 with intact uterus AND amenorrhea for 12 consecutive months or more AND estrogen (estradiol) levels within postmenopausal range; OR
* Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 12 weeks after study drug discontinuation. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. Highly effective contraception methods include:
* Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Use of non-estrogen oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception
* Use of luteinizing hormone-releasing hormone (LHRH) agonist with estrogen level in post-menopausal range and one form of barrier method contraception
* Women who are lactating. Advise lactating women to not breastfeed during treatment and for 1 week after last dose
Liquid Nitrogen Spray Cryotherapy Prior to Neoadjuvant Systemic Therapy in Esophageal Adenocarcinoma
This trial evaluates endoscopic liquid nitrogen spray cryotherapy added to standard neoadjuvant FLOT chemotherapy (with or without the immune checkpoint inhibitor durvalumab) versus chemotherapy alone in patients with locally advanced esophageal adenocarcinoma prior to esophagectomy.
NCT07222657 · Phase 2 · Case Comprehensive Cancer Center
Recruiting sites: Florida
Read full eligibility criteria
Inclusion Criteria:
* Adults with locally advanced EAC who are expected to receive FLOT +/-Durvalumab will be eligible to participate.
* Locally advanced esophageal cancer is defined as TNM stages T1N+M0 or T2-T4aNanyM0, as defined by endoscopic ultrasound (EUS) and PET-CT.
Exclusion Criteria:
* Inability to pass the orogastric decompression tube into the stomach
* Coagulopathy (INR \> 2 or platelet count \< 50,000 per cubic millimeter)
* Inability to provide informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status \> 2
* Risk of thrombosis is determined to be too high to hold anti-platelets (other than aspirin) or anticoagulants prior to the procedure.
Personalized Neoantigen Vaccine Plus IL-12 (INO-9012) Versus Active Surveillance in Subjects With High-Risk HCC
GNOS-PV02, a personalized neoantigen DNA vaccine, combined with INO-9012 (plasmid-encoded IL-12 adjuvant) delivered by intradermal injection with electroporation, is being studied versus active surveillance as adjuvant therapy in high-risk HCC patients with no evidence of disease after definitive resection.
NCT07722741 · Phase 2 · Geneos Therapeutics
Recruiting sites: Georgia, Louisiana, Maryland, Michigan, New York, Texas, Washington
Read full eligibility criteria
Inclusion Criteria:
1. Written informed consent
2. ≥18 years of age
3. Histologically or cytologically confirmed diagnosis of HCC (not accepted: fibrolamellar, sarcomatoid, mixed cholangiocarcinoma)
4. Child-Pugh Class A liver score
5. Documented virology status of hepatitis
6. Availability of a representative post-resection tumor tissue sample
7. ECOG performance status of 0 or 1
8. Adequate organ function
9. Women of childbearing potential (WOCBP) and men must be willing to use an adequate method of contraception
Exclusion Criteria:
1. Is currently participating in and receiving study drug or has participated in a study of an investigational agent and received study drug or used an investigation device, within 4 weeks to baseline
2. Evidence of residual, recurrent, or metastatic disease at randomization
3. Active or history of autoimmune disease or immune deficiency
4. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
5. Diagnosed additional malignancy within 5 years prior to baseline, except for: (a) non-invasive carcinomas subject to successful curative treatment in the opinion of the investigator which require no further therapy and (b) other malignancies for which subjects have undergone potentially curative therapy and have been considered disease free for at least 3 years prior to screening.
6. Active infection requiring systemic therapy
7. Is pregnant, breastfeeding or expecting to conceive or father children within the study's projected duration
8. History of human immunodeficiency virus (HIV) (HIV I/II antibodies).
9. Co-infection with HBV and hepatitis D viral infection
10. Co-infection with HBV and HCV
11. Has received a live vaccine within 30 days of planned start of study
RECTIFY-1: Neoadjuvant Botensilimab + Balstilimab in MSS/pMMR Early Rectal Cancer
Botensilimab (an anti-CTLA-4 antibody, per common knowledge but note the registry text itself does not state mechanism) plus balstilimab (an anti-PD-1 antibody, also not explicitly described by mechanism in the registry) are being studied as neoadjuvant immunotherapy in patients with MSS/pMMR early-stage (T1-T2N0) rectal cancer prior to planned surgical resection.
NCT07735624 · Phase 2 · Dana-Farber Cancer Institute
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
* Histologically confirmed diagnosis of early-rectal cancer clinically staged T1-T2 N0 M0 by MRI (American Joint Committee on Cancer (AJCC) staging 8th edition, 2017).
* The tumor must confirmed to be MSS/MMRp by local testing.
* The tumor must be evaluable by endoscopy.
* Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
* Age ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of botensilimab with balstilimab in participants \< 18 years of age, children are excluded from this study.
* Measurable rectal primary on baseline imaging by MRI. The tumor must be definitively at least T1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function defined as the following laboratory values within 7 days of Cycle 1 Day 1 (C1D1):
* Neutrophils ≥ 1500/μL (Must be stable and off any growth factor within 4 weeks of first study treatment administration).
* Platelets ≥ 50× 103/μL.
* Hemoglobin ≥ 8.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration).
* Creatinine clearance ≥ 30 mL/min as measured or calculated per local institutional standards.
* Aspartate aminotransferase/alanine aminotransferase ≤ 1.5 × upper limit of normal (ULN).
* Total bilirubin ≤ 1.5 × ULN (except patients with Gilbert syndrome who must have a total bilirubin level of ≤ 3.0 × ULN).
* All participants must undergo multidisciplinary evaluation by a qualified colorectal surgeon, medical oncologist, and radiation oncologist to discuss treatment options for rectal cancer.
* Per the treating surgeon, the patient must be a candidate for both TES and/or TME for rectal cancer.
* Per the treating medical oncologist, the patient must be a candidate for standard chemotherapy for rectal cancer.
* Per the treating radiation oncologist, the patient must be a candidate for standard radiation/chemoradiotherapy for rectal cancer.
* The effects of botensilimab with balstilimab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men enrolled in this study must agree to use highly effective contraceptive measures (See Section 3.4) starting with the Screening Visit through 90 days after the last dose of study treatment. See section 3.4 for more detailed information on contraception requirements.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Tumor is MSI-H/MMRd per any local testing.
* Known TMB \>20mut/Mb or indication for immune checkpoint inhibitor therapy including hypermutated cancers.
* Received prior anti-CTLA-4 or anti-PD-1/PD-L1 therapy and/or other experimental immunologic agents.
* Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
* Uncontrolled irritable bowel syndrome with predominant diarrhea (IBS-D) and/or other uncontrolled, chronic diarrhea syndromes.
* Presence of rectal cancer metastases.
* Stigmata of hepatic decompensation including a history of variceal bleeding, a history of ascites related to hepatic cirrhosis, or severe portal hypertension.
* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.
* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Patients with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance, or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
* Treatment with one of the following classes of drugs within the delineated time window prior to C1D1:
* Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
* Investigational monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
* Small molecule/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half- lives of investigational drug.
* Prior therapy for rectal cancer.
* Prior pelvic radiation therapy.
* Prior treatment for rectal cancer.
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
* Any evidence of current interstitial lung disease (ILD) or pneumonitis, or prior history of ILD or non-infectious pneumonitis requiring glucocorticoids.
* History of allogeneic organ transplant.
* Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
* Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mg daily prednisone equivalent) are permitted in the absence of active autoimmune disease.
* Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents or immunosuppressive drugs).
* History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
* Uncontrolled infection with HIV and/or active infection with opportunistic pathogens. Patients stable on antiretroviral therapy with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.
* Known to be positive for HBV surface antigen, or any other positive test for HBV indicating acute or chronic/latent infection. HBV testing is required for study entry.
* Known active HCV as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry.
* History of untreated TB and/or positive quantiferon/Tspot test without previous tuberculosis prophylaxis, or untreated active infection with Mycobacterium tuberculosis. Testing must be negative for study entry.
* Active or known prior infection with nontuberculous mycobacteria.
Samuraciclib for the Treatment of Patients With Resectable, Borderline Resectable, or Locally Advanced Basal Pancreatic Cancer
Samuraciclib, an oral drug whose mechanism/target is not stated in the registry, is being studied as treatment for patients with resectable, borderline resectable, or locally advanced basal-subtype pancreatic ductal adenocarcinoma.
NCT07645651 · Phase 1 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically proven basal pancreatic adenocarcinoma. Histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible.
* Basal tumors are defined as GATA6- and HMGA2+. Tumor cores are considered positive for GATA6 or HMGA2 if greater than 10% of tumor epithelial cells had positive nuclei
* Resectable, borderline resectable, or locally advanced pancreatic ductal adenocarcinoma (PDA) at diagnosis based on contrast-enhanced CT or magnetic resonance imaging (MRI) (CT or MRI without contrast as part of positron emission tomography (PET)/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis. The institutional radiologist must review the scans. Resectable, borderline resectable, and locally advanced will be defined by National Comprehensive Cancer Network (NCCN) guidelines version 2.2025.
* There must be no evidence of metastatic disease
* Must be 18 years or older
* Ability to understand and willingness to sign a written informed consent document
* Archival biopsy specimen collected within 3 months must be available. If not available, a diagnostic EUS/FNB will be performed during screening
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (within 14 days prior to study drug)
* Platelets ≥ 100,000/mcL (within 14 days prior to study drug)
* Hemoglobin ≥ 9 g/dL (within 14 days prior to study drug)
* Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 2.5X ULN (within 14 days prior to study drug)
* Total bilirubin ≤ 1.5X ULN (within 14 days prior to study drug)
* Participants must not be pregnant or nursing. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test within 72 hours of treatment initiation, where WOCBP are defined as all female participants between 18 - 55 years of age. Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception for up to 6 months after the final administered dose of investigational agent. A woman is considered to be of reproductive potential if she has had menses at any time in the preceding 12 consecutive months
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Exclusion Criteria:
* Prior radiation
* Unable to tolerate oral medication, per assessment of the principal investigator (PI)
* Participants who are receiving other investigational agents
* Concomitant mediation use should only exclude patients from trial participation when clinically relevant known or predicted drug-drug interactions or potential overlapping toxicities will impact safety or efficacy
* Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection with clinically significant sequelae that precluded adequate absorption of samuraciclib
* Uncontrolled seizures
* Active infection
* Active bleeding diatheses
* Known active hepatitis B or hepatitis C infection
* Breastfeeding or pregnancy
* Receipt of systemic corticosteroids within 14 days before the first dose of study medication
* Receipt of St. John's Wort within 21 days before the first dose of study medication or of another concomitant medication, herbal supplement, or food that was a strong inhibitor or inducer of CYP3A4, CYP2C19, CYP2D6, or P-glycoprotein activity within 21 days before the first dose of samuraciclib
* Known hypersensitivity to samuraciclib or any excipient of the product
Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC
Zoldonrasib, an investigational RAS(ON) inhibitor, is being studied in combination with pembrolizumab and platinum-based chemotherapy (pemetrexed plus cisplatin/carboplatin) versus placebo plus the same regimen as first-line treatment for metastatic non-squamous RAS G12D-mutated NSCLC.
NCT07777822 · Phase 3 · Revolution Medicines, Inc.
Recruiting sites: Florida
Read full eligibility criteria
Inclusion Criteria:
* At least 18 years old and has provided informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Histologically or cytologically confirmed, previously untreated metastatic non-squamous NSCLC.
* Known PD-L1 status
* Documented RAS G12D mutation status.
* Measurable disease per RECIST v1.1.
* Adequate organ function (bone marrow, liver, kidney, coagulation, thyroid).
* Able to take oral medications.
Exclusion Criteria:
* Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC.
* Prior systemic therapy with any RAS-directed therapy.
* Untreated (symptomatic or asymptomatic) central nervous system metastatic disease.
* Any conditions that may affect the ability to take or absorb study drug.
* Major surgery on or within 28 days prior to randomization.
* Patient is unable or unwilling to comply with protocol-required study visits or procedures.
* Additional inclusion and exclusion criteria may apply
Systemic Anti-Cancer Therapy Dose Modifications for Individuals With Duffy Null Phenotype
This trial applies Duffy-null-specific dose-modification guidelines to standard anticancer regimens (Dara-RVd for multiple myeloma; carboplatin-paclitaxel-pembrolizumab-based KEYNOTE-522 neoadjuvant regimen for TNBC) in patients with Duffy null phenotype receiving first-line treatment for multiple myeloma or Stage II-III triple-negative breast cancer.
NCT07341867 · Phase 1 · Andrew Hantel, MD
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
* Diagnosis of:
* Cohort 1: MM, based on IMWG criteria12, and currently requires treatment
* Cohort 2: Stage II or III TNBC, with definition per protocol Section 3.2.1 AND
* Plan for treatment, per their treating physician, or currently receiving their first cycle (see 3.3.3 for definition) of:
* Cohort 1: Dara-RVd for MM
* Cohort 2: A Keynote 522-based regimen of carboplatin, paclitaxel, and pembrolizumab given as the first phase of neoadjuvant treatment for TNBC.\*\*\*
* Participants are eligible even if the duration of carboplatin and paclitaxel goes beyond 4 cycles, or if the use of pembrolizumab, doxorubicin, and cyclophosphamide is not planned or is not certain, as long as neoadjuvant treatment starts with carboplatin-paclitaxel-pembrolizumab. This cohort will be referred to as "Keynote 522" for the remainder of the protocol.
AND
* Confirmed Duffy null phenotype
* Previous testing is acceptable if performed by a CLIA-approved test
AND
* Age \>=18 years old
Exclusion Criteria:
* Inability to understand and the willingness to sign a written informed consent document
* ANC\<500 within 7 days of planned start of Cycle 1 Day 1.
* Participants who have started treatment at the time of enrollment cannot have started Cycle 2 of therapy
* Participants in Cohort 2 (TNBC) cannot have received any of the pembrolizumab, doxorubicin, and cyclophosphamide portion of therapy
* Participants receiving any other investigational agents for any indication
* Another known condition or medicine with known impacts on neutrophil counts or neutrophil function
A PET Imaging Agent (64Cu-DOTA-Pembrolizumab) for Determining Treatment Response Among Patients With Stage IV Non-small Cell Lung Cancer Receiving Pembrolizumab
This trial uses 64Cu-DOTA-pembrolizumab, a copper-64 radiolabeled version of the anti-PD-1 antibody pembrolizumab, as a PET imaging agent to assess treatment response, while patients continue standard pembrolizumab and receive stereotactic body radiation therapy (SBRT) to oligoprogressive sites, in patients with stage IV non-small cell lung cancer already on pembrolizumab.
NCT07619599 · Phase 1 · City of Hope Medical Center
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Histologically confirmed stage IV non-small cell lung cancer
* Patients on single-agent pembrolizumab, who have been referred for SBRT for or oligo-progressive disease. A maximum of 6 sites will be allowed to receive SBRT on protocol
* Patients must have sites that are amenable to SBRT that are located in lymph nodes, bone/spine, or lung
* Brain metastases or cases with intra-cranial progression are allowed, but an additional extra-cranial site planned for SBRT is required
* Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
* Platelets ≥ 50,000/mm\^3
* NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
* Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN
* Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion Criteria:
* Patient planned to stop pembrolizumab at time of referral for SBRT
* Vaccination with live attenuated vaccines within 4 weeks of study agent administration except forthcoming coronavirus disease 2019 (COVID-19) and flu vaccines
* Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration with the exception of:
* Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
* Chronic systemic corticosteroids at physiologic doses not to exceed 5 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, CT scan premedication)
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Clinically significant uncontrolled illness
* Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment
* Patient unable to tolerate PET scan even with anxiolytic medications
* Other active metastatic malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer (LiGeR-CRC1)
Petosemtamab, a bispecific antibody targeting EGFR and LGR5, combined with chemotherapy (mFOLFOX6 or FOLFIRI) is compared to cetuximab plus chemotherapy as first-line treatment for RAS/BRAF wild-type, unresectable or metastatic left-sided colorectal cancer.
NCT07702032 · Phase 3 · Genmab
Recruiting sites: Arkansas, California, Georgia, Indiana, Missouri, Washington
Read full eligibility criteria
Key Inclusion Criteria:
* Histologically or cytologically confirmed left-sided colorectal adenocarcinoma that is unresectable or metastatic.
* Must have documented KRAS and NRAS wild type (wt) colorectal cancer (CRC), as determined by medical record of results from local testing or as assessed by central testing. Local testing must have been conducted in accordance with local guidelines using an Food and Drug Administration (FDA)-approved test or a laboratory-developed test that is validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States). Next-generation sequencing (NGS)-based test results from tumor tissue are required for determining eligibility. Polymerase chain reaction (PCR)-based tests, sanger sequencing, or pyrosequencing test results are not allowed.
* Has not received any prior systemic therapy for unresectable or metastatic CRC.
* Must be eligible for treatment with mFOLFOX6 (if assigned to receive mFOLFOX6) or FOLFIRI (if assigned to receive FOLFIRI) according to local regulatory approvals and SOC guidelines.
Key Exclusion Criteria:
* BRAF mutation, and/or microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) and/or protocol specified tumor status as documented by local test results in the medical record or from central testing or known documented activating HRAS mutation identified prior to enrollment from local testing results in the medical record, if available.
* Prior exposure to any agents that target epidermal growth factor receptor (EGFR) (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy).
* Known complete dihydropyrimidine dehydrogenase (DPD) deficiency or known homozygous/compound heterozygous dihydropyrimidine dehydrogenase gene (DPYD) variants associated with complete loss of DPD activity. Testing for DPD deficiency should be performed per local guidelines.
* For a participant who is to receive FOLFIRI: known to be homozygous for the UGT1A1\*28 or \*6 alleles or compound or double heterozygous for the UGT1A1\*28 and \*6 alleles. Testing for UGT1A1 should be done in accordance with local guidelines.
* Participants with non-colorectal adenocarcinomatous disease.
Note: Other protocol-defined Inclusion and Exclusion criteria may apply.
A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)
Randomized phase 3 trial adding zanzalintinib, an oral multi-kinase inhibitor (c-Met, VEGFR2, AXL, MER), to belzutifan, a HIF-2alpha inhibitor, versus belzutifan plus placebo in patients with unresectable, advanced clear cell renal cell carcinoma who have had up to 3 prior systemic regimens.
NCT07489495 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Georgia, Kentucky, Massachusetts, Michigan, Missouri, New Jersey, New York, Tennessee
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
* Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
* Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy
Exclusion Criteria:
For exclusion criteria: The main exclusion criteria include but are not limited to the following:
* Has any of the following: a pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
* Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
* Has had major surgery within 8 weeks before randomization
* Has current pneumonitis/interstitial lung disease
* Has a history of human immunodeficiency virus infection
* Has Hepatitis B or Hepatitis C virus infection
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has a history of solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications
A Study of mRNA-4106 or mRNA-4200 Administered Alone or in Combination With Anti-Cancer Agents in Participants With Solid Tumors
mRNA-4106 is given as monotherapy and mRNA-4200 is given in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced or metastatic solid tumors (including cutaneous melanoma, NSCLC, HCC, and other specified carcinomas) who have exhausted or refused standard therapies.
NCT06880549 · Phase 1 · ModernaTX, Inc.
Recruiting sites: California, Michigan, Texas, Utah
Read full eligibility criteria
Key Inclusion Criteria:
* Arm 1: Histologically confirmed advanced or metastatic cancer (cutaneous melanoma, non-small cell lung cancer \[NSCLC\], hepatocellular carcinoma \[HCC\], esophageal carcinoma, head and neck squamous cell carcinoma \[HNSCC\], colon/rectal adenocarcinomas, urothelial/bladder, gastric, ovarian, cervical, and endometrial carcinomas) with measurable disease as determined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) and have completed or refused all standard therapies (no limit to prior lines of therapy). Participants must have a tumor lesion amenable to biopsy, or alternatively archival tumor tissue is acceptable as long as the collection date is within one year of the enrollment date.
* Arm 2: Histologically confirmed advanced or metastatic cancer (cutaneous melanoma, NSCLC, esophageal carcinoma, HNSCC, urothelial/bladder carcinoma, gastric, colon/rectal adenocarcinomas, ovarian, cervical, and endometrial carcinomas \[Note: HCC not included\]) with measurable disease as determined by RECIST v1.1 and have completed or refused all standard therapies (no more than 5 prior lines of therapy in the advanced/metastatic disease setting). Participants must have archival or fresh tumor tissue available for submission at Screening.
* Arm 2: Participant life expectancy of ≥90 days.
* Arm 1 and Arm 2: Participant has an Eastern Cooperative Oncology Group performance status of ≤1.
* Arm 1 and Arm 2: Participant has adequate hematological and biological function.
* Arm 1 and Arm 2: Participants who could become pregnant: negative highly sensitive pregnancy test within 24 hours before the first dose of study treatment.
Key Exclusion Criteria:
* Arm 1 and Arm 2: Participant has active central nervous system tumors or metastases
* Arm 1 and Arm 2: Participant has received treatment with prohibited medications/treatments (that is, concurrent anticancer therapy including other chemotherapy, hormonal anticancer therapy, biologic therapy, or immunotherapy) or investigational agents within 5 half-lives or 14 days prior to the first day of study treatment (Cycle 1 Day 1), whichever is shorter.
* Arm 1 and Arm 2: Participant has required the use of immunosuppressive doses of systemic steroids or absorbed topical steroids (doses \>10 milligrams \[mg\] prednisone daily equivalent) within 2 weeks before study treatment administration or currently requiring maintenance doses of \>10 mg prednisone or equivalent per day.
* Arm 1 and Arm 2: Participant has any plan to receive a live attenuated vaccine during study treatment or has received a live vaccine within 30 days before the first dose of study treatment.
* Arm 1 and Arm 2: Participant has reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline. Any unresolved toxicity National Cancer Institute Common Terminology Criteria for Adverse Events Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and prespecified laboratory values.
* Arm 1 and Arm 2: Participant has any unstable or clinically significant concurrent medical/psychiatric illness or social situation that would limit compliance with study requirements or compromise the ability of the participant to provide written informed consent, per the discretion of the Investigator.
* Arm 1 and Arm 2: Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study).
Note: Other inclusion and exclusion criteria may apply.
A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC)
This phase 3 trial evaluates divarasib, an oral KRAS G12C inhibitor, versus investigator's choice of immunotherapy (pembrolizumab or nivolumab, both PD-1 inhibitors) or observation, as adjuvant treatment in patients with resected Stage II-IIIB KRAS G12C-positive NSCLC who did not achieve pathologic complete response after neoadjuvant chemoimmunotherapy.
NCT07541170 · Phase 3 · Hoffmann-La Roche
Recruiting sites: California, Georgia, Michigan, Nevada, New Mexico
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Histological or cytological diagnosis of clinical Stage II-IIIB NSCLC of either non-squamous or squamous histology
* Participants must have had complete resection of NSCLC
* Prior treatment with neoadjuvant immune checkpoint inhibitor (pembrolizumab or nivolumab) in combination with histology-based platinum-based doublet chemotherapy
* Participants must be randomized within 12 weeks of their surgery date
* No evidence of disease recurrence or metastatic disease
* Documentation of the presence of a KRAS G12C mutation
Exclusion Criteria:
* Participants who achieve pCR following neoadjuvant treatment
* Prior treatment with a KRAS inhibitor or any other anti-cancer therapy not otherwise specified in the protocol
* Prior treatment with radiation therapy for NSCLC, with the exception of localized symptom-directed radiation prior to surgical resection
* Resolved Grade 3 or greater immune-related AE or unresolved Grade 2 or greater immune-related AE from neoadjuvant immunotherapy
* Active or history of autoimmune disease or immune deficiency
* Significant cardiovascular disease
BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases
This trial studies the combination of balstilimab (PD-1 inhibitor), botensilimab (Fc-enhanced CTLA-4 inhibitor), and agenT-797 (allogeneic invariant NKT cell therapy) in previously treated, pMMR/MSS metastatic colorectal cancer with liver metastases.
NCT07550088 · Phase 2 · Darren Sigal, MD
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Adults ≥18 years of age with histologically confirmed metastatic colorectal cancer with liver metastases, including evidence of active liver disease if previously treated locally
* At least one measurable lesion per RECIST v1.1, with ≥1 target lesion in the liver
* Tumor confirmed as microsatellite stable (MSS)/proficient mismatch repair (pMMR) per a FDA-approved assay (Caris MI Cancer Seek®, FoundationOne® CDx, or Tempus xT CDx).
* Received ≥1 prior line of systemic therapy including fluorouracil, oxaliplatin, and irinotecan (not necessarily in combination), and prior EGFR inhibitor or bevacizumab if eligible, unless contraindicated
* ECOG performance status 0-1 and life expectancy ≥12 weeks
* Adequate organ and marrow function:
* ANC ≥1.5 × 10⁹/L
* Platelets ≥100 × 10⁹/L
* Hemoglobin ≥ 9 g/dL
* AST/ALT ≤2.5 × ULN
* Total bilirubin ≤1.5 × ULN
* Creatinine clearance ≥ 40 mL/min, as measured or calculated per local institutional standards.
* Albumin ≥3 g/dL
* PT/PTT ≤1.5 × ULN
* Willing and able to provide written informed consent
* Negative pregnancy test for women of childbearing potential
* Agreement to use effective contraception during study participation
Exclusion Criteria:
* Tumor is dMMR/MSI-high
* Prior treatment with PD-1, PD-L1, CTLA-4 inhibitors, or other immunotherapy agents
* Evidence of bowel obstruction, impending obstruction, or recent obstruction (within 3 months)
* Refractory ascites requiring frequent paracentesis or recent escalation of diuretics
* Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke, unstable angina, NYHA class ≥III heart failure, uncontrolled arrhythmias) or QTc \>480 ms
* Active or untreated brain metastases or leptomeningeal disease
* Concurrent malignancy requiring treatment or active within 2 years (with protocol-specified exceptions)
* Receipt of prior anti-cancer therapy within protocol-defined washout periods, including:
* Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
* Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
* Small molecules/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug.
* Known hypersensitivity to study drugs or excipients
* History of or active interstitial lung disease or pneumonitis requiring systemic steroids
* Prior allogeneic transplant (organ, stem cell, or bone marrow)
* Active or recent autoimmune disease requiring systemic treatment
* Requirement for systemic corticosteroids (\>10 mg prednisone equivalent) or other immunosuppressive therapy within defined windows
* Active infection, including HIV, HTLV, HBV, HCV, or other infections requiring systemic therapy
* Recent SARS-CoV-2 infection within protocol-defined timeframe
* Uncontrolled hypertension, significant proteinuria (UPCR ≥1 g/g), or other clinically significant uncontrolled medical conditions
* Non-healing wounds, active bleeding, or uncontrolled thyroid dysfunction
* Psychiatric or substance use disorders that may interfere with study participation
* Receipt of live or attenuated vaccines within 30 days prior to treatment and while participating in the study
* Pregnant or breastfeeding women, or those planning pregnancy during the study
Dose-Escalation Study of Cabozantinib in Combination With Lutetium-177 (177Lu)-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer
This phase 1 dose-escalation study combines oral cabozantinib (a multi-kinase inhibitor) with the PSMA-targeted radioligand therapy 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who have progressed after novel hormonal therapy.
NCT05613894 · Phase 1 · University of Utah
Recruiting sites: Utah
Read full eligibility criteria
Inclusion Criteria:
* Male subject aged ≥ 18 years.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
* Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
* Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined as second-generation anti-androgen therapies that include, but are not limited to, abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
* Must be eligible for therapy with 177Lu-PSMA-617 and have ≥ 1 PSMA-positive lesion per treating investigator.
* Must have progressive mCRPC per the treating investigator.
* ECOG Performance Status ≤ 1.
* Adequate organ function as defined as:
* Hematologic:
* Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support
* White blood cell count ≥ 3000/µL.
* Platelet count ≥ 100,000/µL
* Hemoglobin ≥ 9g/dL
* Serum albumin ≥ 2.5 g/dl
* PT/INR or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
* Hepatic:
* Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
* For subjects with Gilbert's disease: ≤ 3x ULN
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
* Renal:
* Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
* Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula Males: ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72)
* Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment in accordance with section 5.4.2.
* Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
* Patients must have a life expectancy \>3 months.
Exclusion Criteria:
* Receiving other investigational anti-cancer agents.
* Prior treatment with cabozantinib
* Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization.
* Previous PSMA-targeted radioligand therapy
* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
* Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
* Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment.
* Systemic treatment with radionuclides within 6 weeks before first dose of study treatment.
* Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
* Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis).
* Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment.
* Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
* Major surgery within 4 weeks prior to starting study drug, minor surgery within 10 days, or subjects who have not fully recovered from major surgery.
* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.
* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH)
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
* Cardiovascular disorders:
* Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
* Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before the first dose of study treatment.
* Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion 14) for at least 1 week before first dose of study treatment.
* Uncontrolled hypertension defined as sustained blood pressure (BP) ≥ 150 mm Hg systolic or \>90 mmHg diastolic despite optimal antihypertensive treatment.
* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
* The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
* Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
* Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
* Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.)
* Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
* Lesions invading or encasing any major blood vessels
* Other clinically significant disorders that would preclude safe study participation.
* Serious non-healing wound/ulcer/bone fracture.
* Uncompensated/symptomatic hypothyroidism.
* Moderate to severe hepatic impairment (Child-Pugh B or C).
* Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to first dose of study treatment.
* Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment or minor surgeries within 10 days before first dose of study treatment.
* Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment.
--Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
--Note: If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
* Inability to swallow tablets
* Previously identified allergy or hypersensitivity to components of the study treatment formulations.
* Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
--Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
* Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
* Subjects taking prohibited medications as described in Section 6.8.2. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.
GCCC 2578 Randomized Photon vs Proton RT for Newly Diagnosed Gynecologic Primaries
This trial randomizes patients with newly diagnosed cervical cancer (definitive chemoradiation with HDR brachytherapy boost) or endometrial cancer (post-surgical chemoradiation) to receive external beam radiation via conventional photon-based VMAT versus intensity-modulated proton therapy, each with concurrent weekly cisplatin during EBRT.
NCT07415681 · Phase 2 · University of Maryland, Baltimore
Recruiting sites: Maryland
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Inclusion Criteria:
1. a. Newly diagnosed endometrial cancer after TAH/BSO and nodal sampling, sentinel LN biopsy or pelvic nodal dissection planning to receive sequential chemotherapy and radiation or concurrent chemoradiotherapy or b. cervical cancer planning to receive definitive chemoradiation with HDR brachytherapy boost
2. Histologic confirmation of malignancy (primary only)
3. ≥ 18 years of age
4. ECOG performance status ≤ 2
5. Patient must have the ability to understand and the willingness to sign a written informed consent document or when appropriate, have an acceptable surrogate capable of giving consent on the subject's behalf.
6. Insurance approval for IMPT
Exclusion Criteria:
1. Metastatic disease beyond para-aortic lymph nodal region
2. Residual tumor after surgery exceeding 2 cm in maximum dimension in patients with endometrial cancer.
3. FIGO 2014 stage III-IVA cervix cancer planning to receive concurrent pembrolizumab.
4. Cervical cancer with inability to receive concurrent chemotherapy.
5. Any prior pelvic radiation.
6. Treatment with other investigational agents.
7. Carcinosarcoma.
8. Creatine clearance \<30 mL/m2
9. Unable to lie flat during or tolerate radiation.
10. Refusal to sign informed consent.
11. Any additional active cancer that would interfere with the primary study endpoints
Luminal Bladder Cancer Effective Response to Neoadjuvant Chemotherapy (LUMBER-NAC)
This randomized phase II trial compares standard-of-care neoadjuvant therapy (unspecified regimen) followed by radical cystectomy versus upfront radical cystectomy alone in patients with luminal subtype muscle-invasive bladder cancer.
NCT07762586 · Phase 2 · Rutgers, The State University of New Jersey
Recruiting sites: New Jersey
Read full eligibility criteria
Inclusion Criteria:
* ▪ Inclusion Criteria
* Willing and able to provide informed consent
* Age ≥18 years old
* Eligible to receive standard of care systemic neoadjuvant therapy
* Eastern Cooperative Group (ECOG) performance status of 0-1
* Documented histologically confirmed urothelial muscle-invasive bladder cancer
* cT2N0M0 bladder cancer based on pre-TURBT bimanual exam and cross-sectional imaging performed within 8 weeks of surgery or initiation of NAT.
* Willing to undergo RC with urinary diversion
* No signs of extravesical disease on pre-TURBT conventional imaging
* Variant histology is allowed so long as the tumor is predominantly urothelial carcinoma.
* No presence of LVI on TURBT
* Decipher Bladder GSC test result
* Ineligible for or refusing TMT
* No cN+
* The population is adult men or women of any ethnicity diagnosed with muscle-invasive bladder cancer.
Exclusion Criteria:
* Patients under 18 years old. Considering the minimal incidence of bladder cancer among the pediatric population, children are not eligible for this study.
* Not willing or unable to give informed consent.
* Clinical or pathological evidence of metastatic disease, including, non-regional lymph nodes, visceral lesions, and bone lesions.
* Significant hepatic impairment (Serum bilirubin \> 1.5x upper limit of normal).
* Significant renal impairment (creatinine clearance \<30 ml/min).
* Predominant variant histology (i.e. nested, micropapillary, sarcomatoid, plasmacytoid, small cell)6
* cT3 bladder cancer on pre-TURBT bimanual exam or with hydronephrosis on cross-sectional imaging performed within 8 weeks of surgery or initiation of NAT
* TURBT specimen with lymphovascular invasion (LVI) cT4 or unresectable bladder cancer
* Concurrent diagnoses of other, non-urothelial, malignancies or prior malignancy diagnoses within the past three years. Exceptions, determined at the discretion of the principal investigator, include squamous cell carcinoma, basal cell carcinoma, or other low-grade cancer not expected to progress or require surgical/systemic therapy.
* Prior history of systemic treatment for non-urothelial malignancies in the past three years, including chemotherapy and immunotherapy.
* Prior diagnosis or evidence of psychiatric or medical conditions that may prevent patients from giving full and properly informed consent.
* Any medical, familial, psychiatric, or geographic considerations that may prevent patients from study participation or follow-up required by the study protocol
* Patients (cN+) are excluded from participation and are not eligible for enrollment.
* Prisoners, Individuals without Decisional Capacity, and Pregnant Women will be excluded.
Modulation of the Bone Immune Microenvironment Following Cabozantinib Treatment of Bone Metastatic Clear Cell Renal Cell Carcinoma: Proof of Concept Study
This trial studies cabozantinib (a tyrosine kinase inhibitor per registry drug listing, though specific target not stated) combined with nivolumab (an immunotherapy, target not specified in registry) as first-line systemic treatment in patients with advanced/metastatic clear cell renal cell carcinoma with bone metastases who have had no prior systemic therapy.
NCT07187869 · Phase 1 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
To be eligible for the study, the subject must meet all of the inclusion and none of the exclusion criteria.
1. Signed Written Informed Consent
2. Ability to understand and the willingness to sign a written informed consent document.
3. Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
4. Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and serial biopsy schedule.
5. Participants must be willing to consent to PA-17-0577, a protocol led by Dr. Jianjun Gao, that allows for tissue sample collection and analysis
6. Type of Participant and Target Disease Characteristics
7. Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid or rhabdoid features
8. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
9. No prior systemic therapy with nivolumab or cabozantinib or previous systemic treatment for metastatic disease.
ECOG performance status ≤2 (Karnofsky ≥60%) (See Tables 1 and 2 in section 14 for reference)
10. Presence of both a bone metastasis and visceral or soft tissue metastatic lesion amenable to biopsies
11. Patients must have adequate organ and marrow function as defined below:
* absolute neutrophil count ≥1,000/mcL
* platelets ≥100,000/mcL
* total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (Except participants with Gilbert Syndrome who must have a total bilirubin \< 3.0 x ULN)
* AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
* GFR ≥30 mL/min (using the Cockcroft-Gault formula)
12. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
13. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
14. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Treated CNS metastases are defined as having no ongoing requirement for corticosteroids for at least 2 weeks prior to enrollment and no evidence of progression or hemorrhage after treatment completed at least 4 weeks prior to enrollment clinical examination and brain imaging (MRI or CT).
15. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
16. Patients are eligible to receive standard of care nivolumab and cabozantinib treatment and must be prescribed this regimen at treating physician's determination.
17. Age and Reproductive Status
18. Males and females aged 18 years or greater. Because there is inadequate dosing or adverse event data in patients \<18 years of age, children are excluded from this study.
19. The effects of cabozantinib and nivolumab on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors and immune checkpoint inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation (refer to MDA Policy CLN 1114) and for 4 months after the last dose of cabozantinib and 4 months after the last dose of nivolumab. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.
* In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause).
20. Approved methods of birth control are as follows: Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
21. Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment and 7 months after the last dose of study treatment (ie, 90 days \[duration of sperm turnover\] plus the time required for the investigational drug to undergo approximately five half-lives).
22. Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception which have a failure rate of \< 1% when used consistently and correctly.
Exclusion Criteria:
Any active CNS metastases greater than 0.5cm in size. Participants with treated CNS metastases demonstrated stability for at least 28 days are allowed to enroll.
1. Any impending pathologic fracture or cord compression requiring urgent surgical or site-directed therapy. Participants may be eligible if they undergo initial surgery with tissue collection and have adequately recovered and have received clearance for systemic treatment from orthopedic surgeon or neurosurgery. The tissue collected at the time of initial surgery may be used as the baseline tissue collection. An alternative bone metastasis must be available for biopsy after treatment to be considered eligible.
2. Any active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed.
3. Any tumor invading the GI tract or any evidence of endotracheal or endobronchial tumor within 30 days prior to randomization
4. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
5. Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis, aortic aneurysm, aortic dissection) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
6. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within the past 6 months prior to enrollment
7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of cabozantinib (e.g., malabsorptive disorder, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or small bowel resection)
8. Serious, non-healing wound or ulcer within 2 weeks prior to study enrollment. May be eligible if cleared by surgical team.
9. Evidence of active bleeding or bleeding susceptibility; or medically significant hemorrhage within prior 3 months prior to study enrollment. Microscopic hematuria is allowed.
10. History of cerebrovascular accident (CVA) including transient ischemic attack within the last 6 months prior to enrollment unstable cardiac arrhythmia within 6 months prior to enrollment
11. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \> 450 msec for males and \> 470 msec for females, where QTcF = QT / 3√RR with triplicate measurements
12. Poorly controlled hypertension (defined as systolic blood pressure (SBP) of \> 150 mmHg or diastolic blood pressure (DBP) of \> 90 mmHg), despite antihypertensive therapy
13. History of any of the following cardiovascular conditions within 3 months of study enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure (CHF), as defined by the New York Heart Association (NYHA)
14. Any radiologic or clinical evidence of pancreatitis within 30 days prior to enrollment
15. Inability to swallow oral medications or unwillingness or inability to receive IV administration.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib or other agents used in study.
16. Pregnant women are excluded from this because cabozantinib is a class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib breastfeeding should be discontinued if the mother is treated with cabozantinib. The potential risks may also apply to other agents used in this study.
17. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
18. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection.
19. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
20. Prior/Concomitant Therapy
21. Prior treatment with cabozantinib
22. Concomitant strong CYP3A4 inducers or inhibitors (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort).
23. Concomitant treatment, in therapeutic doses, with warfarin or warfarin-related agents, direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
24. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
25. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
26. Major surgery (e.g., nephrectomy, laminectomy, open pedicle screw stabilization) less than 4 weeks prior to study enrollment. Procedures not classified as major surgery: percutaneous stabilization, kyphoplasty, and laser interstitial thermal therapy (LITT) and can enroll on study 1-2 weeks after procedure.
27. Physical and Laboratory Test Findings
28. WBC \< 2000/μL
29. Neutrophils \< 1500/μL
30. Platelets \< 100 x 103/μL
31. Hemoglobin \< 9.0 g/dL (support with transfusion is acceptable)
32. Calculated creatinine clearance \< 20 mL/min (using the Cockcroft-Gault formula)
33. AST/ALT \> 3.0 x ULN
34. Total bilirubin \> 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 x ULN)
35. Urine protein/creatinine ratio (UPCR) ≥ 1.0, unless 24-hour urine protein is \< 1.0 g
36. INR \> 1.6
37. History of allergy or hypersensitivity to study drug components
38. History of severe hypersensitivity to a monoclonal antibody
39. Other Exclusion Criteria
40. Prisoners or participants who are involuntarily incarcerated.
41. Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Neoadjuvant Dupilumab and Toripalimab in MSS CRC Subjects With Resectable Liver Metastases
Neoadjuvant combination of dupilumab and toripalimab (a PD-1 immune checkpoint inhibitor; dupilumab's mechanism/target not stated in this record) given before planned surgery in microsatellite-stable colorectal cancer patients with resectable liver metastases.
NCT07277322 · Phase 1/2 · Dan Feng
Recruiting sites: New York
Read full eligibility criteria
INCLUSION CRITERIA:
Histological diagnosis of non-MSI-H/pMMR CRC
• Subjects who have biology-proven non-MSI-H/pMMR CRC and with radiographic findings suggestive of liver metastases may be eligible.
Resectable liver metastases including:
* synchronous liver metastases (present at the time of diagnosis of MSS CRC) and treatment-naïve
* metachronous liver metastasis (developed after resection of the primary tumor) without prior adjuvant chemotherapy
* metachronous liver metastasis (developed after resection of the primary tumor) with adjuvant chemotherapy completed greater than 3 months from the time of consent.
Surgical candidate for resection
Age ≥ 18 years. Rationale: Because no dosing or adverse event data are currently available on the use of dupilumab in combination with toripalimab in subjects \<18 years of age, children are excluded from this study.
ECOG Performance Status 0-1 (Karnofsky ≥60%,)
• Subjects with performance status \>1 carrying long-term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy may be enrolled at the investigator's discretion
Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception upon study entry, for the duration of study participation, and for 3 months following completion of therapy.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Ability to understand and the willingness to sign a written informed consent. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Adequate organ and marrow function as defined:
* Hematologic
o Absolute neutrophil count (ANC) ≥1,000 /mcL
* Platelets ≥75,000 /mcL
* Hemoglobin ≥8 g/dL
* Renal\* o Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated (Creatinine clearance should be calculated per institutional standard) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥45 mL/min for subjects with creatinine levels \> 1.5 X institutional ULN
* Hepatic\* o Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN; ≤ 3 X ULN for subjects with liver metastases o AST ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
* ALT ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
* Albumin \>2.5 mg/dL
* Coagulation\*
* International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants
* Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants \* If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert's syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the lab values will not be used to exclude subject from this trial. This determination will be made by PI.
EXCLUSION CRITERIA:
History of autoimmune disorder with the following exceptions:
* Vitiligo, alopecia, psoriasis or any chronic skin condition that does not require systemic therapy
* Hypothyroidism (e.g. following autoimmune thyroiditis) stable on thyroid replacement
* Celiac disease controlled by diet alone
Treatment, for any reason, with an immunomodulatory drug, within 8 weeks from time of consent.
Prior treatment with dupilumab within the last 8 weeks.
Prior treatment with chemotherapy for MSS CRC or locoregional therapy to the target lesion (that will be biopsied and subsequently resected) within 3 months prior to entering the study.
• Previous therapy for a different cancer (a different primary) is acceptable.
Use of investigational agents for treatment of cancer.
Subjects with extrahepatic metastases that are not amendable to resectable or locoregional therapy, for whom the intent of surgery would not be curative.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements, as determined the treating investigator.
Pregnant or nursing women due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Breastfeeding should be discontinued prior to study enrollment.
Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Chronic steroids equivalent to ≤ 10mg prednisone are permitted.
Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
Has a known additional malignancy that is progressing and requires active treatment.
• Exceptions include: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA, and breast cancer treated with curative intent now on hormonal therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<200 CD4+ T cells/microliter in the peripheral blood. HIV testing is mandatory for patients with no known history of HIV. For such patients, HIV testing will be considered SOC.
Has known active Hepatitis B (e.g., HBV detected by PCR (\>200 IU/ml) or known active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Subjects who started antiviral therapy \>/=14days from baseline are permitted.
History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps) Principle investigator believes that for one or multiple reasons the subject will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the subject.
Phase 1 Study Of Izalontamab Brengitecan + Adagrasib In NSCLC - The IZA-A Trial
This trial evaluates the combination of Izalontamab Brengitecan (Iza-bren) and the KRAS G12C inhibitor Adagrasib in patients with advanced KRAS G12C-mutant NSCLC who have progressed on a prior KRAS G12C inhibitor (registry does not specify Iza-bren's mechanism/target).
NCT07382726 · Phase 1 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed diagnosis of NSCLC or NSCLC predominant histology.
* Patients must have a diagnosis of metastatic or locally advanced NSCLC not amenable to curative therapy
* Tumor must harbor a KRAS G12C mutation. Testing available through multigene NGS panels performed in the Molecular Diagnostics Laboratory in UT MD Anderson Cancer Center and can be performed using either tissue or blood assays. Use of standard of care (SOC) results are allowed to meet this requirement.
* Patients must have progressed on a prior KRAS G12C inhibitor as monotherapy or as combination therapy.
* Patients must have received at least one prior line of therapy and up to 3 prior lines of therapy.
* Patients must have measurable disease per RECIST v1.1.
* Age ≥18 years - no dosing or adverse event data are currently available on the use of izabren and adagrasib in patients \<18 years of age; children are excluded from this study.
* ECOG performance status 0 - 1.
* Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) discontinued at least 2 weeks before first dose date.
* Most recent radiation treatment discontinued at least 1 week prior to first dose date (includes brain radiation).
* Patients must have adequate organ and marrow function as defined below:
Hemoglobin ≥9.0g/dL Absolute neutrophil count ≥1,500/mcL Platelets ≥100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN (if associated with liver metastases, ≤ 5 x ULN) Creatinine ≤ 1.5 mg/dL or CrCl ≥ 45 mL/min (calculated using a validated prediction equation - e.g., Cockcroft-Gault, MDRD, or 24-hour urine CrCl)
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable.
* Patients with a history of hepatitis C virus (HCV) infection must have documentation of undetectable HCV viral load.
* Patients with treated brain metastases are eligible if patients are neurologically stable for at least 1 week prior to the first dose of study treatment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
* Because adagrasib and iza-bren are known to be teratogenic, women of child-bearing potential (WCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 (men) and 7 (WCBP) months after completion of study treatment administration. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients less than 55 years of age unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.
* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of study treatment administration.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) except for alopecia and parameters superseded by other eligibility criteria \[e.g., laboratory parameters\]).
* Patients who are receiving any other investigational agents.
* Patients with active untreated brain metastases or carcinomatous meningitis.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to adagrasib and iza-bren.
* Patients with prior history of pneumonitis or interstitial lung disease. Patients with prior history of radiation pneumonitis which was asymptomatic or resolved with steroid treatment, and without evidence of clinically active radiation pneumonitis are eligible.
* Human immunodeficiency virus (HIV)-infected patients. Those on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Patients with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant and actively breastfeeding woman due to concerns for teratogenicity and infant toxicity.
* Major surgery within 4 weeks prior to first dose of study treatment.
* History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
* Prolonged QTc interval (\>470 milliseconds for women and \>450 milliseconds for men), or immediate family or medical history of congenital Long QT Syndrome.
* History of stroke or transient ischemic attack within 6 months prior to first dose of study treatment.
* History of unstable angina, myocardial infarction, and symptomatic atrial fibrillation within 6 months prior to first dose of study treatment.
* Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.
Phase 1 Study to Assess Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of ARR-002 in Advanced or Metastatic Ovarian or Endometrial Cancer.
ARR-002 is a novel agent whose precise mechanism/target is not explicitly stated in the registry (though exclusion criteria barring prior auristatin-derived, MUC16-, or NaPi2b-targeted agents suggest a related class), being tested in a Phase 1 trial for advanced/metastatic ovarian (including platinum-resistant) and endometrial cancer.
NCT07755436 · Phase 1 · ArriVent BioPharma, Inc.
Recruiting sites: Florida, Massachusetts, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Patients with histologically and cytologically confirmed advanced or metastatic ovarian, primary peritoneal, or fallopian tube cancer, and platinum resistant who have failed or intolerant to standard therapy, or without alternative standard therapy.
* Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
* Tumor specimen available for testing, or agree to biopsy at baseline.
* The score of Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy ≥ 12 weeks.
* Organ functions and coagulation function must meet the basic requirements.
* Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.
Exclusion Criteria:
* Prior treatment with auristatin-derived drugs s (eg, MMAE and monomethyl auristatin F \[MMAF\]).
* Received antitumor therapy within 4 weeks prior to the first dose or 5 half-lives, whichever is shorter.
* Infection of active hepatitis B, active hepatitis C, or HIV.
* Symptomatic Central nervous system and/or meninges metastasis.
* History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months before the first dose of study treatment.
* Previous drug-induced interstitial lung disease (ILD) or active ILD.
* Poorly controlled pleural, peritoneal, and pelvic effusion, or combined pericardial effusion.
* History of recurrent gastrointestinal (GI) obstruction.
* Patients with more than one cancer.
* Any other diseases, pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding
* Grade ≥ 2 peripheral neuropathy
* History of severe cardiovascular diseases.
* Current use of anticoagulants or thrombolytic agents for therapeutic purposes.
* Known allergic reactions to any component of ARR-002.
* Prior treatment with MUC16- or NaPi2b-targeting agents.
* Ocular conditions such as keratitis or corneal ulceration, monocularity, corneal transplantation, uncontrolled retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder.
* Other situations that are not suitable to participate a clinical trial per investigator's judgement.
Phase 1, Safety and Tolerability Study of XmAb541 and XmAb808 in Advanced Solid Tumors
XmAb541 and XmAb808, bispecific monoclonal antibodies (XmAb541 targeting CLDN6+ tumors), are being tested in combination as a Phase 1 dose-finding/safety study in patients with locally advanced, recurrent, or metastatic high-grade serous ovarian carcinoma (including fallopian tube or primary peritoneal origin).
NCT07593092 · Phase 1 · Xencor, Inc.
Recruiting sites: New York, Texas
Read full eligibility criteria
Inclusion Criteria:
* Age ≥ 18 years.
* CLDN6+ tumor
* Histological or cytological documentation of locally advanced, recurrent, or metastatic high grade serous ovarian carcinoma (HGSOC) including fallopian tube or primary peritoneal origin
* Adequate Eastern Cooperative Oncology Group performance status
* Life expectancy ≥ 3 months
* Adequate organ function
Exclusion Criteria:
* Prior exposure to a CLDN6 targeting immune cell engager
* Patients with treated brain metastases may participate, provided they are radiologically stable.
* Active known or suspected autoimmune disease
* Have any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug
* Clinically significant cardiovascular, pulmonary or gastrointestinal disease
* Active viral hepatitis B or hepatitis C
Study of TUB-040 Given With Standard Ovarian Cancer Drugs in Patients With Fast-growing Ovarian Cancer
TUB-040 (mechanism/target not stated in the registry) is being studied in combination with carboplatin and bevacizumab in patients with platinum-sensitive, high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer that has progressed after prior therapy.
NCT07736937 · Phase 1/2 · Tubulis GmbH
Recruiting sites: California, New Jersey, New York
Read full eligibility criteria
Inclusion Criteria:
1. Female ≥ 18 years of age at the time of the first screening visit
2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
3. Histologically confirmed advanced high-grade serous or endometrioid epithelial ovarian, fallopian tube or primary peritoneal cancer.
4. Have platinum-sensitive ovarian cancer (PSOC) defined as: Patients who had recurrences (radiologically confirmed) to platinum-based therapy and have responded to the last platinum therapy received before study entry and did not progress within 6 months (182 days) of the date of the last dose of platinum-based systemic treatment.
5. Radiologically measurable disease in at least 1 lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, that can include a lesion in an irradiated field and that shows progression according to RECIST v1.1
6. Patients must have progressed radiographically on or after their most recent line of anticancer therapy
7. Adequate hematologic function as indicated by:
1. Platelet counts ≥100,000/mm3 (no transfusion or growth factors, e.g., eltrombopag, romiplostim, or IL-11 within 4 weeks before first dose)
2. Hemoglobin ≥9.0 g/dL (no transfusion or growth factors e.g. erythropoietin (EPO), darbepoetin within 4 weeks before first dose or long-acting white blood cell growth factors within 20 days before first dose)
3. Absolute neutrophil count (ANC) ≥1500/μL (no growth factors, e.g., granulocyte colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF) within 4 weeks before first dose)
4. International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN) in the absence of anticoagulation therapy. If patients are on anticoagulation therapy with a specific INR goal, INR should be within the therapeutic range for the medical indication.
8. Adequate hepatic function defined as total bilirubin level ≤1.5 × ULN, an aspartate aminotransferase (AST) level ≤2.5 × ULN, and an alanine aminotransferase (ALT) level ≤2.5 × ULN
1. For documented Gilbert's Syndrome, a total bilirubin \<3 × ULN is accepted
2. For patients with liver metastases, AST and ALT \<5 × ULN is accepted
9. Alkaline phosphatase \< 2.5 x ULN, except if there is an alternative explanation for ALP elevation rather than hepatic failure, such as the presence of bone metastasis
10. Adequate renal function defined by glomerular filtration rate ≥60 mL/min (according to the Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, formula \[Appendix B\]).
11. Patients must be willing to sign an archival tissue release form for research purposes and determination of biomarker (e.g., NaPi2b) expression. The patient must have an adequate tumor tissue sample available for biomarker assessment by the central laboratory. Mandatory is either a tissue (FFPE) block or a minimum of 6 freshly cut unstained sections based on the most recently available tumor sample. If no archival specimens are available, a new biopsy must be performed. For patients in which a fresh biopsy poses unacceptable clinical risk in the judgment of the treating investigator, enrollment may be considered on a case-by-case basis only after discussion with the Sponsor Medical Monitor.
12. Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade ≤1 including peripheral neuropathy (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone) replacement, corticosteroid treatment on ≤10 mg daily prednisone (or equivalent)
13. Patients with previous systemic topoisomerase 1 inhibitor treatment (e.g., Topotecan) or patients that are previously treated with ADCs are allowed (except for ADCs with a topoisomerase 1 inhibitor, such as SN38 or other camptothecin derivatives as payload or any ADC targeting NaPi2b)
14. Completed washout of prior therapy:
1. Systemic anti-neoplastic therapy: five half-lives or 4 weeks, whichever is shorter prior to first dose of study drug. Hormonal therapy is not considered anti-neoplastic therapy.
2. Radiotherapy: last dose ≥ 2 weeks from first dose of study drug
3. Completed major surgery at least 4 weeks prior from first dose of study drug and recovered from side effects to Grade ≤1.
15. Viral infections:
1. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load Note: Patients should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post-completion of study intervention.
2. Patients with history of hepatitis C viral (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Patients must have completed curative anti-viral therapy at least 4 weeks before enrollment
16. Women of childbearing potential (WOCBP) who are sexually active with a non-sterilized partner must use at least 1 highly effective method of contraception (with a failure rate of ≤1% per year) from the time of screening and must agree to continue using such precautions until the end of exposure, plus at minimum 5 half-lives and 6 months after last dose of either TUB-040, carboplatin, or bevacizumab, whichever is later, in the case of patients of childbearing potential. Abstinence is acceptable only when this is in line with the preferred and usual lifestyle of the patient for the duration of the study treatment and the above-referred period after the end of the exposure. Periodic abstinence (e.g. calendar ovulation, symptom-thermal, post-ovulation methods), the rhythm method, and the withdrawal method are not acceptable methods of contraception.
Note: A pregnancy test (urine or serum test or per institutional guideline) 72 hours before enrollment is required in WOCBP. Within 72 hours before enrollment, if a positive urine pregnancy test result is confirmed using a serum test, then the patient should not be enrolled into the study. Pregnancy tests (urine or serum test per institutional guideline) should be performed within 72h and resulted prior to the administration of any study treatment, at End of Treatment, and during Follow-Up as mandated by the Schedule of Assessments. In Follow-Up, this is continued monthly for 5-half-lives + 6 months after the last dose of any drug under study, at minimum. Women who have undergone a hysterectomy and/or bilateral salpingo-oophorectomy are exempted from testing.
17. Patients must agree to continue a highly effective contraceptive method, refrain from egg cell donation and breastfeeding while on study treatment and for 5 half-lives plus 6 months after the last dose of study treatment.
Note: The half-life of TUB-040 is approximately 6 days.
18. Female patients will be considered post-menopausal if they have undergone bilateral salpingectomy, and/or bilateral oophorectomy, and/or hysterectomy or have been amenorrheic for 12 months without an alternative medical cause (treatment with antihormonal therapies is considered an alternative medical cause). The following age specific requirements apply:
1. Women \<50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all hormonal replacement therapy and/or if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution.
2. Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all hormonal replacement therapy or had radiation-induced menopause with most recent menses \>1 year ago or had chemotherapy-induced menopause with most recent menses \>1 year ago.
19. In the opinion of the INV, the patient must be able to understand, must be willing to sign informed consent form (ICF) and comply with all study-related procedures, medication use, and evaluations.
20. Patients must have 1-2 prior lines of systemic platinum therapy and have not progressed within 182 days after the date of the last dose of platinum.
Notes:
I. Neoadjuvant ± adjuvant is considered as one line of therapy.
II. Maintenance therapy (e.g., BEV, poly adenosine diphosphate-ribose polymerase inhibitors (PARPi)) does not count as a line of therapy.
III. Prior treatment may include BEV
21. Prior treatment with PARPi is required (for patients who were previously documented to be HRD positive or have a germline or somatic BRCA 1/2 mutation), if PARPi therapy was locally approved at the time of testing.
Exclusion Criteria:
1. Patients with clear-cell, mucinous histology, mixed histology with mucinous component, sarcoma, sarcomatous component, or low-grade ovarian cancer
2. Patients with platinum refractory ovarian cancer (OC) (Platinum refractory is defined as disease that has not responded to a primary platinum-based regimen or progressed within 30 days after primary platinum-based therapy) or platinum resistant ovarian cancer
3. Patient pregnant, lactating or breastfeeding or having a positive serum pregnancy test during the screening period
4. Previous systemic topoisomerase-1 inhibitor treatment (except Topotecan)
5. History of hypersensitivity to monoclonal antibodies, exatecan or excipients of the TUB-040 formulation.
Note: The excipients of TUB-040 are listed in the IB.
6. Patients with unresolved malignant bowel obstruction (including patients with radiological findings indicating possible bowel obstruction on CT scans), history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess or Patients on total parenteral nutrition (TPN)
7. Prior thoracocentesis for therapeutic drainage of malignant effusion \< 4 weeks from trial inclusion and repeated paracentesis for therapeutic drainage of malignant effusion \< 4 weeks before trial inclusion
8. Prior radiotherapy to the pelvis or abdomen (Dose Escalation phase only)
9. Patients with serum albumin level \<2,5 g/dL (subjects should not have received IV albumin within 4 weeks of the test)
10. Participation in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives (whichever is shorter) of any investigational pharmacologic agents before study treatment
11. Patients with untreated spinal cord compression or cerebrovascular accident/stroke within \<6 months of enrollment
12. Major surgery within 21 days prior to signing the ICF, unless the patient is recovered at that time
13. History of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis
14. Documented cardiac comorbidities: Corrected QT interval \> 470 msec on the screening ECG, unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, uncontrollable hypertension (≥Grade 3), uncontrollable arrhythmias, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV) or severe aortic stenosis
15. Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary (including liver cirrhosis), cardiovascular, respiratory, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the INV, would predispose the patient to the development of complications from the administration of protocol therapy
16. Demyelinating diseases: History of multiple sclerosis or of progressive multifocal leukoencephalopathy
17. History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
18. Any concurrent anti-cancer chemotherapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticosteroid therapy, other than that permitted in Section 8.8.
19. Live vaccines within 30 days prior to study entry or any known unresolved and active bacterial, viral (e.g. Hep B, Hep C, Varicella or CMV), fungal, mycobacterial, or other infection at screening
20. History of hypersensitivity to Carbo and risk of further cumulative toxicity with additional platinum, including but not limited to myelosuppression, with febrile neutropenia, Grade 4 hematotoxicity, neuropathy Grade ≥2, renal insufficiency during prior platinum-based therapy
21. Non-healing wounds, ulcers, or bone fractures
22. History of posterior reversible encephalopathy syndrome
23. Recent history of hemoptysis of ≥1/2 teaspoon of red blood within 4 weeks before first study treatment,
24. History of Grade 4 thromboembolic events
25. Hypertension ≥ Grade 3 that is not controlled with medical management
26. Clinically significant proteinuria: urine-protein (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and must show result \< 1 gram of protein in 24-hour period.
27. Any patient who is required to take strong CYP3A4 inhibitors or inducers (see also Prohibited Medication and Guidance for Potential Use section).
1. Note: If it is clinically acceptable to replace such medication with a different medication which is not a strong CYP3A4 inhibitor or inducer, then the patient may be eligible.
Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer
This phase I trial evaluates the oral BET bromodomain inhibitor ZEN-3694 combined with the MEK1/2 inhibitor binimetinib in patients with advanced/metastatic or unresectable solid tumors bearing RAS-pathway alterations or triple-negative breast cancer.
NCT05111561 · Phase 1 · National Cancer Institute (NCI)
Recruiting sites: Massachusetts, Texas
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically confirmed advanced/metastatic or unresectable solid tumor that is refractory to standard therapy or has relapsed after standard therapy
* Patients must have one of the following:
* For Part 1 and 2 -
* Triple negative breast cancer (TNBC) (estrogen receptor =\< 1%, progesterone receptor =\< 1%, human epidermal growth factor receptor 2 0-1+ or non-amplified)
* Solid tumor with genomic alteration(s) activating RAS signaling including activating KRAS, NRAS, HRAS, or BRAF mutations, inactivating NF1 mutations, or BRAF fusions
* Genomic alterations should be identified locally by next generation sequencing (NGS). Patient genomic reports will be reviewed by the MD Anderson Cancer Center (MDACC) Precision Oncology Decision Support team prior to initiation of study treatment
* For Part 1, patients can have evaluable or measurable disease. For Part 2, patients must have measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Patients must be \>= 4 weeks beyond treatment with any chemotherapy (6 weeks for nitrosoureas or mitomycin C) or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of study treatment initiation. Patients must be \>= 4 weeks beyond radiotherapy
* Age \>= 18 years. Because no dosing or adverse events (AE) data are currently available on the use of binimetinib and ZEN003694 (ZEN-3694) in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 125,000/mcL
* Hemoglobin \>= 8 g/dL or \>= 5.6 mmol/L
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) OR \< 2.0 x ULN in patients with documented Gilbert's syndrome
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
* Calculated creatinine clearance \>= 60 mL/min/1.73 m\^2 (based on the calculated Chronic Kidney Disease-Epidemiology collaboration \[CKD-EPI\] glomerular filtration rate estimation)
* Prothrombin time =\< 1.5 x ULN
* Partial thromboplastin time =\< 1.5 x ULN
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to the first dose of study treatment. This exception does not include carcinomatous meningitis and primary CNS cancers, which are excluded regardless of clinical stability
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study
* Patients should be New York Heart Association Functional Classification of class 2B or better
* Patients must have corrected QT (QTcF) \< 450 msec
* The effects of ZEN003694 (ZEN-3694) and binimetinib on the developing human fetus are unknown. For this reason and because BETi agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after the completion of ZEN003694 (ZEN-3694) and binimetinib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ZEN003694 (ZEN-3694) and binimetinib administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients who have not recovered from adverse events (AEs) due to prior anticancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia, peripheral neuropathy, and endocrinopathy managed with replacement therapy before the initiation of study treatment
* Patients who are receiving any other investigational agents
* Breast cancer patients with a prior history of hormone receptor positivity will not be eligible
* Patients with known PI3K pathway activating genomic alterations including inactivating mutations/deletions in PTEN and PIK3R1, amplifications in PIK3CA, and activating mutations in PIK3CA, Akt, or mTOR will not be eligible
* Prior therapy with BET, RAF, MEK, or ERK inhibitor
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) and binimetinib
* Patients requiring therapeutic doses of anticoagulation are excluded. Patients taking low-dose (prophylactic) anticoagulation (e.g., low-molecular weight heparin, low-dose warfarin, fondaparinux) are allowed. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers). As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) and binimetinib are a BETi and MEK inhibitor agent, respectively, with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694) and binimetinib, breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694) and binimetinib
* Patient has a history of cerebrovascular accident, myocardial infarction, or unstable angina within the previous 6 months prior to study treatment initiation
* Patients with any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g., gastrectomy, ileal bypass, chronic diarrhea, gastroparesis) are excluded
* Patient has a history of retinal vein occlusion
* Patient has a history of pneumonitis or interstitial lung disease
A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer
VS-7375, an oral small-molecule inhibitor of both active (GTP-bound) and inactive (GDP-bound) KRAS G12D, is being studied alone or in combination with cetuximab in patients with previously treated, unresectable locally advanced or metastatic KRAS G12D-mutated non-small cell lung cancer.
NCT07659782 · Phase 2 · Verastem, Inc.
Recruiting sites: Arizona, California, Colorado, Florida, Georgia, Illinois, New Jersey, New York, North Carolina, Texas, Utah, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Histopathology confirmed unresectable locally advanced or metastatic NSCLC
* Measurable disease per RECIST 1.1
* Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
* ECOG PS=0 or 1
* Adequate organ function
* Received prior treatment with a platinum-based chemotherapy regimen and an immune checkpoint inhibitor in the advanced, non-resectable setting.
* Have documented disease progression during or following their most recent prior line of therapy.
Patients with 2L/3L on stable or preferred dose:
* Received at least 1 and no more than 2 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.
Patients with 2L-4L with brain metastases:
* Received at least 1 and no more than 3 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.
* Have asymptomatic and untreated brain metastases
* At least 1 untreated measurable brain lesion per mRECIST v1.1 with a long axis ≥ 0.5 cm and ≤ 3 cm.
Exclusion Criteria:
* Have any other documented co-existing common RAS mutation(s)
* Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
* Major surgery within 4 weeks of first treatment dose
* Radiation therapy (RT) within 1 week of first treatment dose
* History of drug-induced Interstitial Lung Disease
* Receipt of prior direct RAS inhibitor
* Untreated or symptomatic CNS metastasis
* Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
* Receipt of PPI or H2 blocker within 5 days
* Inability to swallow oral medication
* Other protocol-defined inclusion/exclusion criteria may apply
A Study in Patients With Metastatic Castration-Resistant Prostate Cancer
FX-111 is an orally administered investigational agent (mechanism/target not specified in the registry) being studied in a Phase 1 trial for adult men with metastatic castration-resistant prostate cancer who progressed on ADT and a prior AR pathway inhibitor.
NCT07719361 · Phase 1 · Flare Therapeutics Inc.
Recruiting sites: California, Massachusetts, Michigan, New Jersey, South Carolina, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria:
* Confirmed adenocarcinoma of the prostate.
* PSA levels ≥ 2 ng/mL at screening visit.
* Progressing PSA, defined as two consecutive increases in the most recent PSA measurements taken at least 1 week apart.
* Progressed on Androgen Deprivation Therapy (ADT) and at least one prior potent Androgen Receptor (AR) pathway inhibitor given in castration-sensitive prostate cancer setting or approved for castration-resistant prostate cancer (eg, apalutamide, darolutamide, abiraterone, enzalutamide).
* Ongoing primary ADT with gonadotropin-releasing hormone agonist or antagonist in the absence of bilateral orchiectomy.
* Acceptable physical functioning and laboratory measurements, per the study protocol.
* Discontinued prior therapies within protocol-specified timeframes.
* Commit to use of highly-effective contraception while on study and for 90 days after.
* Willing and able to adhere to the study visit schedule and other protocol defined requirements.
Exclusion Criteria:
* Predominance of small cell carcinoma of the prostate/neuroendocrine prostate cancer in most recent tumor biopsy.
* Participants with brain metastases that require ongoing treatment with radiation or high-dose steroids.
* Not recovered from side effects of prior surgery or cancer treatments.
* Evidence of active viral, bacterial, or fungal infection requiring treatment with antivirals, antibiotics, or anti-fungal medications.
* Prior treatment with AR degraders and molecules with an AR ligand such as AR Regulated Induced Proximity Targeting Chimera (RIPTAC).
* Blood clots ≤ 4 weeks prior to start of treatment.
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study drug. Patients may be eligible if the malignancy is clinically stable or has been treated with curative intent.
* Any evidence of severe or uncontrolled systemic diseases.
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.
A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)
BMS-986504, an oral PRMT5 inhibitor selective for MTAP-deleted cancer cells, is being studied as monotherapy and in combination regimens in advanced/metastatic solid tumors with homozygous MTAP deletion.
NCT07492680 · Phase 2 · Bristol-Myers Squibb
Recruiting sites: California, Colorado, Georgia, Maryland, Massachusetts, Michigan, Minnesota, New York, North Carolina, Texas, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
* Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease.
* Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline.
* Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer must be ≤ 2 × ULN.
* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria:
* Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor.
* Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
* Participants must not have history of gastrointestinal disease or other gastrointestinal conditions within 6 months prior to enrollment (including uncontrolled nausea, vomiting, malabsorption syndrome or non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess) likely to alter absorption of study treatment or result in inability to swallow oral medications.
* Participants must not have inadequate organ function, as determined by laboratory testing within the screening period.
* Participants must not have active viral HBV or HCV hepatitis.
* Other protocol defined inclusion/exclusion criteria applies.
A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors
ARV-6723 is an investigational oral agent (mechanism not specified in the registry, though prior anti-HPK1 therapy is an exclusion criterion) given alone or with the anti-PD-1 antibody pembrolizumab in a first-in-human Phase 1/2 study of adults with advanced/metastatic solid tumors who have progressed after prior immune checkpoint inhibitor therapy.
NCT07749586 · Phase 1/2 · Arvinas Inc.
Recruiting sites: New York, North Carolina, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
Part A1 dose escalation and A2 dose optimization: Participants must meet all of the following criteria:
* Have a histologic or cytologic diagnosis of unresectable or metastatic solid tumor malignancy.
* Have previously received at least one prior therapy targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and/or another T-cell co-stimulatory or immune checkpoint pathway, in any treatment setting (including neoadjuvant or adjuvant).
* Have received prior SOC therapy appropriate for their disease type and stage and have no remaining available treatment options with established clinical benefit; or, in the opinion of the investigator, are unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy; or have declined SOC therapy.
* Participants must have demonstrated radiographic progression and have at least 1 measurable lesion per RECIST v1.1 that has not been previously irradiated or has demonstrated progression of disease since radiation therapy.
* ECOG PS 0 or 1 or equivalent. Participants with ECOG PS 2 may be considered upon discussion with the Sponsor Medical Monitor.
* Participants with adequate organ function.
Exclusion Criteria:
Exclusion Criteria (Part A)
* Active brain metastases (new lesions identified on imaging, existing lesions showing progression per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)/imaging characteristics or by clinical criteria, lesions requiring active interventions for symptom control).
* Carcinomatous meningitis.
* Known or suspected hypersensitivity to ARV-6723 or pembrolizumab or any of its excipients.
* Active autoimmune disease or history of autoimmune diseases that may relapse.
* History of severe immune-related adverse events (irAE) attributed to prior anti-PD-1/anti-CTLA-4/anti-LAG-3 therapy.
* Prior treatment with any HPK1-targeting agent
* Systemic anti-cancer therapy or radiation therapy within 14 days prior to study treatment start.
* Current use of any prohibited concomitant medication(s) or herbal supplements which cannot be discontinued, prior to start of study intervention and for the duration of the study.
* Baseline (screening) standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
A Study to Evaluate Adverse Events and Change in Disease Activity of Intravenous ABBV-706 Versus Standard of Care in Adult Participants With Relapsed/Refractory Small Cell Lung Cancer
ABBV-706, an SEZ6-targeted antibody-drug conjugate delivering a topoisomerase 1 inhibitor, is being compared to standard chemotherapy (topotecan, lurbinectedin, or amrubicin) in adults with relapsed/refractory small cell lung cancer.
NCT07365241 · Phase 3 · AbbVie
Recruiting sites: Alabama, Arizona, California, Florida, Georgia, Illinois, Indiana, Kentucky, Massachusetts, Michigan, Minnesota, New Jersey, North Carolina, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Virginia, West Virginia, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Diagnosis of histologically or cytologically confirmed Relapsed/Refractory (R/R) Small Cell Lung Cancer (SCLC).
* Participants must have progressed on prior systemic therapy, with CPI (if eligible) and prior tarlatamab, defined as:
* In the 1L and 2L setting respectively, platinum-based chemotherapy (i.e., carboplatin or cisplatin and etoposide with CPI, if eligible for CPI) and 2L tarlatamab; or
* In the 1L and 2L setting, platinum-based chemotherapy (i.e., carboplatin and etoposide with atezolizumab and lurbinectedin in combination with atezolizumab maintenance and 2L tarlatamab; or
* In the 1L setting, platinum-based chemotherapy (i.e., carboplatin or cisplatin and etoposide with CPI if eligible) in combination with tarlatamab in frontline induction and/or maintenance
* Participants must be considered suitable to receive SOC comparator (topotecan, lurbinectedin, or amrubicin).
* Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 during the screening period prior to the first dose of study treatment.
* Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participants with brain metastasis from an extracranial solid tumor are eligible if the brain metastases are:
* Previously treated and not requiring anticonvulsants and steroids for at least 7 days prior to first dose of study treatment. If required for management, subjects on a steroid equivalent of prednisone dose of ≤ 10 mg/day are eligible or;
* Untreated and asymptomatic not requiring anticonvulsants and steroids for at least 7 days prior to the first dose of study treatment. If required for management, subjects on a steroid equivalent of prednisone of ≤ 10 mg/day are eligible.
Exclusion Criteria:
* Participants with known active/symptomatic central nervous system metastases.
* Participants with a history of interstitial lung disease (ILD) or pneumonitis that previously required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan.
* Participants with any clinically significant conditions that would adversely affect the participation in the study, and the subject should have a life expectancy of at least 3 months.
* Participants who have received prior treatment with a seizure-related 6 homolog (SEZ6) targeted Antibody drug conjugate (ADC), other targeted ADCs, or any other investigational agent not including tarlatamab in 1L.
* Participants who have received prior treatment with any Top1i such as topotecan, irinotecan, belotecan, camptothecin, rubitecan, exatecan or locally approved topoisomerase I inhibitor (Top1i) payload.
Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial
This trial evaluates consolidative local therapy (IMRT/VMAT or SBRT to residual sites, radiosensitizing chemotherapy, and/or radical cystectomy with pelvic lymphadenectomy) added after response to enfortumab vedotin plus pembrolizumab in patients with muscle invasive (locally advanced or oligometastatic) bladder cancer.
NCT07579195 · Phase 1/2 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Age \>= 18 at the time of screening
* Ability to understand and willingness to sign a written informed consent document
* Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis
* Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro
* If M1 after completion of EV + pembro, patients need to have =\< 5 sites of metastasis and all sites of metastasis should be extracranial
* Note: when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastatic lesions, etc). Five or fewer sites of metastasis applies after the completion of EV + pembro, not at initial diagnosis
* Be a candidate for consolidative radiation therapy (RT) to the pelvis (if indicated) or cystectomy (if indicated), and all sites of metastasis are amenable to RT
* Life expectancy \> 6 months
* Eastern Cooperative Oncology Group (ECOG) performance 0-2
* Absolute neutrophil count (ANC) \>= 1500 /mcL (within 180 days of trial registration)
* Platelets \>= 100,000/mcL (within 180 days of trial registration)
* Hemoglobin \> 9 g/dL (within 180 days of trial registration)
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR \>= 60 mL/min (within 180 days of trial registration)
* Total bilirubin =\< 1.5 ULN OR direct bilirubin =\< ULN if total bilirubin \> 1.5 x ULN (within 180 days of trial registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN OR \< 5 x ULN if patient has live metastasis (within 180 days of trial registration)
* Albumin \>= 2.5 g/dL (within 180 days of trial registration)
* International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless on anticoagulation therapy, in which case PT or partial thromboplastin time (PTT) should be in the therapeutic range (within 180 days of trial registration)
* PTT =\< 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range (within 180 days of trial registration)
* Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception during, and for at least 90 days after the end of radiation therapy. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours of treatment initiation
* HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial
Exclusion Criteria:
* Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation
* Intracranial metastasis
* Any small cell component, or predominant (\> 50%) sarcomatoid or plasmacytoid histology
* Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator
* Genetic conditions that increase sensitivity to radiation, such as Fanconi syndrome, ataxia telangiectasia, and Nijmegen breakage syndrome
* Active human immunodeficiency virus (HIV) not adequately controlled, active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected), as determined by standard of care testing
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Any other medical condition that may interfere with trial therapy delivery
* Adults with impaired decision-making capacity, as determined by the treating physician
DSP-0390 in Combination With Atezolizumab for Small Cell Lung Cancer
DSP-0390, an EBP (emopamil-binding protein) inhibitor blocking de novo cholesterol synthesis, is combined with the anti-PD-L1 antibody atezolizumab as maintenance therapy in extensive-stage small cell lung cancer patients who have not progressed after first-line platinum-based chemoimmunotherapy.
NCT07545954 · Phase 1 · Washington University School of Medicine
Recruiting sites: Missouri
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed small cell lung cancer.
* Completed 3-4 cycles of induction chemoimmunotherapy as first line treatment of ES-SCLC without disease progression.
* Measurable disease per RECIST 1.1.
* At least 18 years of age.
* ECOG performance status ≤ 2
* Adequate bone marrow and organ function as defined below:
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 100 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN (≤ 5.0 x IULN for patients with liver metastases)
* Calculated creatinine clearance \> 40 mL/min by Cockcroft-Gault
* The effects of DSP-0390 on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use adequate contraception prior to study entry, for the duration of study treatment, and for 6 months after the last dose of DSP-0390.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition (following discussion with the PI) are eligible for this trial
* Currently receiving any other investigational agents, or received within 4 weeks prior to Day 1 (unless investigational immunotherapy, which may not have been received within 6 weeks prior to Day 1).
* Patients with untreated symptomatic brain metastases or with clinically evident CNS hemorrhage. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression. Patients with asymptomatic, punctate brain metastases \< 5 mm are allowed.
* Known contraindications to use of PD-L1 inhibitor as assessed by the treating physician.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DSP-0390 or atezolizumab.
* Undergone major surgery within 28 days prior to Cycle 1 Day 1.
* Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1.
* Patient is known to have short-gut syndrome, or other condition that may significantly limit the ingestion or gastrointestinal absorption of drugs administered orally.
* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
* Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
* Concurrent use of prohibited medications: carbamazepine, phenytoin, phenobarbital, other strong or moderate CYP3A4 inhibitor or inducer, or strong CYP2D6 inhibitors. These should be discontinued 1 week or 5 half-lives (whichever is greater) prior to study day 1. Note that both oral and IV ondansetron at doses ≤ 8 mg Q6h are permitted.
* Patient has a clinically significant abnormal ECG, including those where QT prolongation is determined by the Fridericia formula (QTcF \>450 msec for males and \>470 msec for females); and/or the patient has a history of Torsade de Pointes.
IGFBP-2 Vaccine to Prevent Ovarian Cancer Progression in Patients With Serologic Detection of Recurrence
IGFBP-2 multi-epitope plasmid DNA vaccine given intradermally after a single dose of carboplatin, studied to prevent progression in ovarian, fallopian tube, or primary peritoneal cancer patients with serologic (CA-125) recurrence after platinum-based chemotherapy but no measurable disease.
NCT07495124 · Phase 2 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Have a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer who have received systemic chemotherapy including platinum-based chemotherapy
* Have a cancer antigen 125 (CA-125) that normalized after first-line therapy
* CA-125 increased to more than twice the upper limit of normal or two times the nadir value after most recent second or later line of treatment
* Have no measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Ascites and pleural effusions are not measurable disease, if asymptomatic
* All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of the study (end of one year follow up). Note: Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or postmenopausal
* Have estimated life expectancy of at least 3 months
* Be willing and able to provide written informed consent/assent for the trial
* Be ≥ 18 years of age on day of signing informed consent
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
* White blood cell (WBC) ≥ 3000/mm\^3 (performed within 14 days of treatment initiation)
* Hemoglobin (Hgb) ≥ 10 g/dl (performed within 14 days of treatment initiation)
* Hematocrit (Hct) ≥ 28% (performed within 14 days of treatment initiation)
* Serum creatinine ≤ 2.0 mg/dl or creatinine clearance \> 60 mL/min (performed within 14 days of treatment initiation)
* Total bilirubin ≤ 2.5 mg/dl (performed within 14 days of treatment initiation)
* Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal (ULN) (performed within 14 days of treatment initiation)
* Blood glucose \< 1.5 ULN (performed within 14 days of treatment initiation)
Exclusion Criteria:
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of treatment (i.e., day 1)
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (if dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
* Short-term administration of systemic steroids (i.e., for allergic reactions or the management of immune-related adverse events \[irAEs\]) is allowed
* Has symptomatic ascites or pleural effusions
* History of borderline or low malignant potential ovarian cancer
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
* Has had prior chemotherapy, biologic therapy, targeted small molecule therapy, hormonal therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent
* Note: Patients with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study
* Note: If a patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Has an active infection requiring systemic therapy
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
* Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
* Clinically significant cardiovascular disease
* Known severe hypersensitivity reactions to carboplatin ≥ grade 3, any history of anaphylaxis, or uncontrolled asthma
* Patients with any contraindication to receiving recombinant human granulocyte macrophage-colony stimulating factor (rhuGM-CSF) based products
* Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
* Has known active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis c virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
* Has received a live vaccine or live-attenuated vaccine within 30 days of planned start of study therapy. Administration of killed vaccines is allowed
* Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
MRI-based Focal Intraprostatic Simultaneous Integrated Boost (SIB) Intensification With De-escalated Adaptive-risk SBRT for Patients With Low to Intermediate Risk Prostate Cancer
This trial uses MRI-guided stereotactic body radiation therapy with a focal intraprostatic simultaneous integrated boost (microboost SBRT to 45 Gy) plus dose-de-escalated whole-gland SBRT (30 or 35 Gy) as primary treatment for patients with low- to intermediate-risk localized prostate cancer.
NCT07644598 · Phase 2 · Georgetown University
Recruiting sites: District of Columbia
Read full eligibility criteria
Inclusion Criteria:
1. Patients age 18 or older.
2. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
3. Patients with histologically confirmed adenocarcinoma of the prostate who have not received prior pelvic radiation therapy or prostatectomy.
4. Patients with low to intermediate risk group defined by the NCCN (National Comprehensive Cancer Network) guidelines as follows:
* Low risk prostate cancer:
* cT1-cT2a (AJCC; 8TH edition, 2017)
* Grade Group 1 (GG1)
* PSA \<10 ng/mL
* Intermediate risk prostate cancer:
* cT2b-cT2c (AJCC; 8TH edition, 2017)
* Grade Group 2 (GG2) or Grade Group 3 (GG3)
* PSA 10-20 ng/mL
5. Patients with unfavorable intermediate risk prostate cancer defined by the NCCN guidelines are recommended to undergo a PSMA (Prostate-Specific Membrane Antigen) PET, then the PSMA PET must show localized disease.
6. Patients must have preferably undergone a standard of care pretreatment MRI fusion biopsy\* to identify visible intraprostatic lesions and confirm the absence of regional or distant metastatic disease, with criteria as follows:
* Ability to undergo an MRI fusion biopsy;
* Prostate size \<100 cc on any diagnostic MRI;
* Presence of a visible prostatic lesion:
* PIRADS (Prostate Imaging-Reporting and Data System) 4+ lesion, and/or
* PIRADS 3 lesion with evidence of grade group 2-3
* Less than or equal to 4 lesions in total allowed;
* Lesion may contact the capsular edge, "possible" extracapsular extension (ECE) permitted; \*MRI fusion biopsy is preferred but if the positive core is in the same region as the target on the MRI based on a systemic biopsy, the patient can be included.
7. Genitourinary function with a baseline score ≤20 as defined by any pre-treatment IPSS questionnaire.
8. Patients are mandated to get a fiducial placement. Optional proper rectal spacer placement is recommended as determined by the treating radiation oncologist based upon whether there is overt rectal wall invasion from the hydrogel spacer or if there is minimal to no separation of the prostate-rectal interface measured at the prostate mid-gland.
9. Patients with a life expectancy of greater than 5 years as assessment by the investigator. Life expectancy can be estimated using any 1 of the following tools:
* The Social Security Administration tables: https://www.ssa.gov/OACT/STATS/table4c6.html
* The WHO's Life Tables by country: https://apps.who.int/gho/data/view.main.60000?lang=en
* The Memorial Sloan Kettering Male Life Expectancy tool: https://www.mskcc.org/nomograms/prostate
* If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information.
10. Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:
* With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method, which together result in a failure rate of \< 1% per year, during the treatment period and for 1 year after treatment per local and institutional guidelines. Men must refrain from donating sperm during this same period.
* With a pregnant female partner, men must remain abstinent or use a condom during the treatment period per local and institutional guidelines to avoid potential exposure to the embryo.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.
11. Patients who are able to give informed consent.
Exclusion Criteria:
1. Patients with evidence of disease Grade Group 4 (GG4) or higher.
2. Patients with PSA \>20 ng/mL.
3. Patients with evidence of clinical stage T3a+ or gross extracapsular extension on the diagnostic MRI.
4. Patients who received prior or concurrent androgen deprivation therapy for prostate cancer.
5. Patients with more than 4 disease foci identifiable on MRI.
6. Patients with evidence of metastatic disease on imaging (e.g., bone scan, PSMA PET scan, or MRI/CT scan).
7. Patients with ineligibility to undergo an MRI due to:
* The presence of a cardiac pacemaker, defibrillator, or other implanted metallic or electronic device which is considered MRI unsafe;
* Severe claustrophobia;
* Inability to lie flat for the duration of the study;
* Metallic implant or device in the pelvis that might distort the local magnetic field and compromise quality of MRI;
* Any other reason as determined by the investigator or treating physician.
8. Patients with an I-PSS score \>20 as defined by any pre-treatment IPSS questionnaire.
9. Patients with a prior history of transurethral resection of the prostate, TURP, Urolift, or other similar trans-urethral LUTS management procedure within the last 6 months.
10. Patients with a prior history of severe urethral stricture.
11. Patients with a prior history of pelvic irradiation.
12. Patients unable to meet dosimetric constraints
13. Patients with a prior history of non-cutaneous solid malignancy within the last 5 years.
14. Patients with a history of active and uncontrolled inflammatory bowel disease.
15. Patients who are unable to comply with follow-up visits and treatment plans.
Phase 1/2 Study of Intravenous Injection of STX-003 in Advanced Solid Tumors as Monotherapy or in Combination With Pembrolizumab
STX-003, an IV-delivered self-replicating mRNA encoding IL-12 (with miRNA-sensing target sites), is being studied as monotherapy or combined with the PD-1 inhibitor pembrolizumab in patients with advanced solid tumors, including specified cohorts of advanced cutaneous melanoma and PD-L1+ NSCLC, in a first-in-human Phase 1/2 treatment trial.
NCT07751042 · Phase 1/2 · Strand Therapeutics Inc.
Recruiting sites: Arizona, Massachusetts, Tennessee
Read full eligibility criteria
Inclusion Criteria:
* Inclusion Criteria (Phase 1 and Phase 2)
1. Mentally competent and able to understand and sign the ICF.
2. Tumor type for which there is an FDA-approved anti-PD-1/L1 antibody therapy, specifically including biomarker labeled subsets (i.e. PD-L1+) as well as anatomical subsets in some disease (cutaneous melanoma is eligible whereas acral, mucosal and uveal are not; Phase 1) and advanced cutaneous melanoma or PD-L1+ NSCLC.
3. Histologically or cytologically documented, locally advanced, or metastatic solid tumor.
4. At least one measurable lesion per RECIST v1.1 criteria.
5. The patient lacks a curative therapy or has progressive disease despite, or refused, standard therapy.
6. ECOG performance status of 0 or 1.
7. Life expectancy of ≥ 12 weeks per the Investigator.
8. ≥ 18 years of age at the time of informed consent.
9. Body weight ≥ 40 kg.
10. WOCBP and males with female partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months following the last dose of STX-003.
11. Willing and able to comply with protocol required assessments.
Hematology:
* ANC ≥ 1,000 cells/mm3.
* Platelet count ≥ 75,000 cells/mm3.
* Hemoglobin ≥ 8.0 g/dL.
* Renal: Serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation
Coagulation:
* PT/INR or PT must be ≤ 1.5 × ULN.
* aPTT ≤ 1.5 × ULN unless undergoing anticoagulation therapy.
• Liver:
* Albumin ≥ 3.5 g/dL or within the normal range of the local reference laboratory.
* AST and ALT \< 2 × ULN.
* Bilirubin ≤ 1.5 × ULN (except participants with documented Gilbert's syndrome who may be enrolled if the conjugated bilirubin is within normal limits) or ≤ 5 × ULN with liver metastases.
Phase 2 Inclusion Criteria
13\. NSCLC :
* Histologically or cytologically documented findings consistent with NSCLC not amenable to curative surgery, radiation, or other therapy.
* Biomarker confirmed as PD-L1+ per local institutional standard practice.
* Patients with known activating EGFR, STK11 or KEAP1 mutations as well as ALK/ROS1 fusions, are not eligible.
* Prior treatment (for advanced, metastatic or \[neo\]adjuvant) should have included a platinum-based therapy and a PD-1/L1 pathway checkpoint inhibitor, unless the patient is not a candidate for or has refused viable therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity).
14\. Melanoma : Histologically or cytologically documented findings consistent with advanced cutaneous melanoma not amenable to curative surgery, radiation, or other therapy. Acral, mucosal and uveal melanoma are excluded.
* Patients who are not candidates for or have refused available therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity) are also eligible.
* Received an anti-PD-1/PD-L1 inhibitor as monotherapy or in combination with anti-CTLA-4 inhibitor and have either primary or secondary checkpoint inhibitor resistance asper SITC consensus definition, unless deemed intolerable by the Investigator. Patients with BRAF V600E mutant melanoma should have received a BRAF inhibitor as monotherapy or in combination with other targeted agents (MAPK kinase MEK inhibitors), unless deemed intolerable by the Investigator.
Exclusion Criteria:
* Exclusion Criteria (Phase 1 and 2)
1. Medical Conditions
* History of primary immune deficiency.
* History of clinically significant autoimmune disease that has required intervention in the last 6 months. Consultation with the MM may inform the discussion of whether autoimmune disease is clinically significant.
* History of Grade 3 or higher IRAEs that has not resolved to Grade ≤ 1 at the time of enrollment. Exceptions include endocrine disorders that are well-managed with stable physiological hormone replacement and Grade 3 immune-related rash. Patients meeting this criterion may be considered for enrollment following approval by the MM.
* History of solid organ transplant and taking immunosuppressive medications.
2. Cardiovascular exclusions
* Medical history of an arterial thrombotic event, stroke, or transient ischemic attack within the past 6 months.
* Medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a cardiac arrhythmia that required treatment within the past 6 months.
* Medical history of myocardial infarction or unstable angina within 6 months before C1D1.
3. Recent medical concerns exclusions
* Evidence of active infection requiring IV antibiotics within 7 days prior to C1D1.
* Active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to C1D1.
* Serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to C1D1.
* Known HIV infection, active hepatitis B infection, or hepatitis C infection:
* Virology evaluation should be conducted at Screening to include serum HIV antibody, HBc antibody, HBsAg antigen, and HCV antibody. Patients with a positive antibody evaluation for HCV and/or HBc should undergo evaluation to measure HCV RNA or HBV DNA, respectively.
* Untreated CNS tumor, epidural tumor or metastasis, or brain metastasis. Patients with any primary CNS malignancy including glioma and current, active, or progressing CNS malignancy, including carcinomatosis meningitis, are excluded.
* Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening period and are off systemic steroids (for at least 2 weeks prior to first dose).
* Another primary malignancy that has not been treated with curative intent (discuss with MM), except for non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
* Serious illness considered by the Investigator as incompatible with participating in this clinical study.
* Major surgery within 4 weeks of first dose of study drug.
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patients' safety or study results.
4\. Prior/Concomitant Therapy
* Prior treatment with STX-003 or other VEEV-based replicating RNA.
* Prior IL-12 therapy.
* Receipt of any live vaccine within 30 days prior to the first dose of study treatment.
* Use of another systemic anticancer therapy within 3 weeks prior to C1D1 or 5 halflives, whichever is shorter or use of radiotherapy within 1 week prior to C1D1 5. Prior/Concurrent Clinical Study Experience
* Previously enrolled in this study.
* Actively enrolled in another clinical study unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study.
* Known severe hypersensitivity (Grade ≥ 3) to study treatment or any of the excipients of the products.
Other Exclusions
* History of interstitial lung disease or active, non-infectious pneumonitis (combination cohorts only).
* Known psychiatric or substance use disorder that would interfere with the patient's ability to cooperate with the requirements of the study.
* Currently pregnant (confirmed with a positive pregnancy test), breast-feeding or planning to become pregnant within 6 months following treatment. For WOCBP, a negative serum β-HCG result must be available within a 72-hour window before the first treatment dose.
Phase 2A Pilot C3 Trial of Recurrent/Refractory Metastatic Advanced Pancreatic Cancer
This trial studies gemcitabine combined with repurposed drugs metformin, simvastatin, and digoxin (C3) — or C3 alone if gemcitabine is declined — as treatment in patients with recurrent/refractory metastatic advanced pancreatic cancer who have progressed after at least one prior standard regimen.
NCT06030622 · Phase 1/2 · State University of New York - Downstate Medical Center
Recruiting sites: New York
Read full eligibility criteria
Inclusion Criteria:
1. Subject ≥18 years with histologically confirmed pancreatic cancer.
2. Refractory, intolerant to, or with disease progression after at least one standard of care regimen.
3. ECOG performance status (PS) 0-1.
4. Pretreatment biopsy and/or adequate archival tissue available for BIRC5 protein level evaluation.
5. Adequate organ and marrow function: absolute granulocyte count ≥1,000/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutional upper normal limit, AST/ALT ≤2x institutional upper limit of normal, and creatinine \<1.5 mg/dL or calculated creatinine clearance \> 60ml / min (Cockcroft-Gault Equation).
6. Subject has recovered to CTCAE Grade 1 (except for alopecia) or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
7. If participant of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. Serum pregnancy tests will be conducted at the time of screening, when other blood draws are obtained (See Appendix III: Time-Table of Procedures).
8. Ability to understand and the willingness to sign a written informed protocol specific consent.
9. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
10. No known active infections at the time of enrollment as determined by negative procalcitonin level.
Exclusion Criteria:
1. Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first investigational product administration.
2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
4. Known history of rhabdomyolysis.
5. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the Investigator.
6. Known chronic Hepatitis B or C infection.
7. Have current active infection requiring systemic antibiotic treatment.
8. History of severe allergic, anaphylactic, hypersensitivity reactions or previous intolerance to Metformin, Simvastatin, and/or Digoxin.
9. Patients with significant cardiac disease or condition listed below (unless clearance obtained by cardiology):
1. Wolff-Parkinson-White Syndrome.
2. Previous MI within last 6 months of C1D1.
3. Evidence of residual electrographic pattern consistent with heart block., for example atrio-ventricular (AV) heart block (currently ongoing).
4. History of ventricular fibrillation.
5. Sick Sinus Syndrome or Sinus bradycardia thought to be caused by sinus node disease, unless effectively treated.
6. Heart failure with preserved LVEF, including constructive pericarditis, and amyloid heart disease.
10. Acute cor pulmonale, restrictive cardiomyopathy, and Amyloid heart muscle disease.
11. Participants of childbearing potential who are found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) or nursing.
12. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or trial results.
13. Cognitively impaired and diminished capacity.
Pre-operative Atezolizumab in Patients With Resectable, Human Papillomavirus Related Oropharyngeal Carcinoma
Preoperative atezolizumab (a PD-L1 immune checkpoint inhibitor biologic) is given prior to transoral surgery and neck dissection in patients with resectable, HPV-related, Stage I oropharyngeal squamous cell carcinoma.
NCT06254911 · Phase 2 · Emory University
Recruiting sites: Georgia
Read full eligibility criteria
Inclusion Criteria:
* The subject is \>= 18 years old on the day of consent
* Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 5 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 5 months after the last dose of study drug(s).
* Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
* A male participant must agree to use a contraception as detailed in this protocol during the treatment period and for at least during the active treatment plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose\] after the last dose of study treatment and refrain from donating sperm during this period.
* The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oropharynx, Stage 1 (T1/2 N1) Squamous Cell Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a clinical laboratory improvement act (CLIA) approved laboratory.
* Patients must not have evidence of extensive or "matted/ fixed" pathologic adenopathy on preoperative imaging.
* The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of therapy
* The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
* Criteria related to comparator drug or background therapy, if applicable: No prior radiation above the clavicles. Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer
* Age \>= 18 years at time of signing Informed Consent Form
* Ability to comply with the study protocol
* Histologically or cytologically confirmed p16+ HPV-driven OPSCC
* Availability of a representative tumor specimen for exploratory biomarker research
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/GL) without granulocyte colony-stimulating factor support obtained within 14 days prior to initiation of study treatment
* Lymphocyte count \>= 0.5 x 10\^9/L (500/GL) obtained within 14 days prior to initiation of study treatment
* Platelet count \>= 100 x 10\^9/L (100,000/GL) without transfusion obtained within 14 days prior to initiation of study treatment
* Hemoglobin \>= 90 g/L (9 g/dL) obtained within 14 days prior to initiation of study treatment.
* Patients may be transfused to meet this criterion
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) =\< 2.5 x upper limit of normal (ULN), obtained within 14 days prior to initiation of study treatment with the following exceptions:
* Patients with documented liver metastases: AST and ALT =\< 5 x ULN
* Patients with documented liver or bone metastases: ALP =\< 5 x ULN
* Serum bilirubin =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment with the following exception:
* Patients with known Gilbert disease: serum bilirubin =\< 3 x ULN
* Serum creatinine =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
* Serum albumin \>= 25 g/L (2.5 g/dL) obtained within 14 days prior to initiation of study treatment
* For patients not receiving therapeutic anticoagulation: international normalization ratio (INR) or activated partial thromboplastin time (aPTT) =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
* Negative human immunodeficiency virus (HIV) test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Negative hepatitis B surface antigen (HBsAg) test at screening
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from study entry:
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
* Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Active tuberculosis
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Patients requiring pain medication must be on a stable regimen at study entry
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX) are allowed.
* Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12mg/dL or corrected serum calcium \>ULN)
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety.
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* History of malignancy must have been treated with curative intent and must be disease free for 1 year prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma
* Prior allogeneic stem cell or solid organ transplantation
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
* Current treatment with anti-viral therapy for HBV
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
* Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment
* Glomerular filtration rate \< 29 mL/min/1.73 m\^2 as calculated through use of the Chronic Kidney Disease Epidemiology Collaboration equation
* An ANC \< 1.5 x 10\^9/L (1500/GL) with one exception:
* Patients with benign ethnic neutropenia (BEN): ANC \< 1.3 x 10\^9/L (1300GL) BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups
Pressurized Intraperitoneal Aerosolized Nab-Paclitaxel in Combination With Gemcitabine and Cisplatin for the Treatment of Biliary Tract Cancer Patients With Peritoneal Metastases
This phase I trial studies nab-paclitaxel delivered via pressurized intraperitoneal aerosolized chemotherapy (PIPAC) combined with IV gemcitabine and cisplatin in patients with biliary tract cancer (intrahepatic/extrahepatic cholangiocarcinoma or gallbladder cancer) that has metastasized to the peritoneum.
NCT05285358 · Phase 1 · City of Hope Medical Center
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies
* If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma or gallbladder cancer
* Documented metastatic disease on computed tomography (CT) imaging or magnetic resonance imaging (MRI). CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
* Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
* Fully recovered from acute toxic effects (except alopecia, hearing loss, or non-clinically significant laboratory abnormalities) =\< grade 1 of prior anti-cancer therapy
* Complete medical history and physical exam (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Platelets \>= 100,000/mcL (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Hemoglobin \>= 8 g/dL (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Serum albumin \>= 2.8 g/dL (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, then direct bilirubin \< 1.5 mg/dL) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Aspartate aminotransferase (AST) =\< 5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Alanine aminotransferase (ALT) =\< 5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Calculated creatinine clearance of \>= 45 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* If seropositive, patient may be eligible if they are stable on antiretroviral therapy, have a CD4 T cell count \>= 200/µL, and have an undetectable viral load
* Documented virology status of hepatitis, confirmed by hepatitis B virus (HBV) and hepatitis C virus (HCV) tests (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* For patients with active HBV, HBV deoxyribonucleic acid (DNA) \< 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to day 1 of cycle 1, and willingness to continue anti-HBV treatment during the study (per standard of care)
* If seropositive for HCV, nucleic acid quantification must be performed. Viral load must be undetectable
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential\* to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion Criteria:
* Any prior systemic therapy treatment for advanced cholangiocarcinoma or gallbladder cancer
* Any prior adjuvant therapy (chemotherapy, radiation therapy, biological therapy, immunotherapy) completed \< 6 months prior to registration
* Strong CYP3A4 inducers/inhibitors within 14 days prior to day 1 of protocol therapy
* Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy, or exclusive total parenteral nutrition
* Evidence of liver metastases with \>= 50% liver occupation
* Any history of, or current, brain or subdural metastases
* Life expectancy \< 3 months
* History of peripheral neuropathy \>= grade 2 measured by NCI CTCAE version 5.0 ("moderate symptoms, limiting instrumental activities of daily living")
* Treatment with therapeutic oral or IV antibiotics within 14 days prior to day 1 cycle 1 of treatment
* Patients receiving prophylactic antibiotics are eligible, provided the signs of active infection have resolved
* Any prior malignancy except adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents (platinum-based compounds, etc.)
* Clinically significant uncontrolled illness
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
REGN15505 (PSMAx4-1BB) Alone or in Combination With Cemiplimab or REGN4336 (PSMAxCD3) in Adult Patients With Metastatic Castration-Resistant Prostate Cancer and Clear Cell Renal Cell Carcinoma
REGN15505, a PSMA x 4-1BB bispecific immune-costimulatory antibody, is being studied alone or combined with the anti-PD-1 antibody cemiplimab or the PSMA x CD3 bispecific REGN4336 in previously treated metastatic castration-resistant prostate cancer and metastatic clear cell renal cell carcinoma.
NCT07594106 · Phase 1/2 · Regeneron Pharmaceuticals
Recruiting sites: Arizona, California, Florida, Illinois, Missouri, Texas
Read full eligibility criteria
Key Inclusion Criteria:
Participants with mCRPC:
1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
2. mCRPC with PSA value at screening ≥4 ng/mL and that has progressed within 6 months prior to screening as described in the protocol
3. Has received ≥2 lines of prior systemic therapy approved in the metastatic and/or castration-resistant setting as described in the protocol
4. Have had either Orchiectomy or be on Luteinizing Hormone-Releasing Hormone (LHRH) agonist or antagonist therapy with serum testosterone \<50 ng/dL AND agree to stay on LHRH agonist or antagonist therapy during the study
Participants with ccRCC:
5. Men and women with histologically or cytologically confirmed Renal Cell Carcinoma (RCC) with a clear-cell component
6. Diagnosis of metastatic ccRCC with at least 1 measurable lesion via Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
7. Has progressed on or after ≥1 line of prior systemic therapy approved in the metastatic setting. Prior treatment must include an Anti Program Cell Death 1 (PD-1)/ Program Death Ligand 1 (PD-L1) therapy and either ipilimumab and/or a Tyrosine Kinase Inhibitor (TKI)
Key Exclusion Criteria:
For Both mCRPC and ccRCC Cohorts:
1. Has received treatment with an approved systemic therapy (including sipuleucel-T for mCRPC patients) within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in the protocol
mCRPC Cohort Only:
2. Has received prior Prostate Specific Membrane Antigen (PSMA)-targeting therapy with the exception of a PSMA-targeting radioligand (eg, 177Lu-PSMA-617)
Note: Other protocol defined inclusion/exclusion criteria apply
RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
This trial compares RO7771950 (mechanism not stated in the registry) plus trastuzumab and capecitabine versus tucatinib (a HER2 tyrosine kinase inhibitor) plus trastuzumab and capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer who have received prior anti-HER2 therapy.
NCT07413939 · Phase 2/3 · Hoffmann-La Roche
Recruiting sites: Alabama, Arizona, California, Connecticut, New Jersey, New York, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria:
* Pathologically documented locally advanced inoperable (LAI) or metastatic breast cancer (MBC) with confirmed HER2-positive status by central laboratory.
* Measurable disease as per by RECIST v1.1 in stage 1. Non-measurable disease allowed in stage 2.
* Previously treated (stable or progressive) or previously untreated CNS metastases, or leptomeningeal metastases.
* At least one prior line of anti-HER2-based therapy for LAI or metastatic disease.
* Prior anti-HER2 antibody-drug conjugate (ADC), such as trastuzumab-deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1), in any treatment setting. Participants without prior ADC therapy may only be enrolled if approved standard-of-care (SOC) anti-HER2 ADC is not locally accessible at screening, or if there is a prospectively documented clinical contraindication.
* Prior tyrosine kinase inhibitor (TKI) in the (neo)adjuvant setting provided completion is \> 12 months ahead of LAI occurrence. Prior treatment with TKIs for LAI/MBC is not permitted.
* Has protocol-defined adequate organ and bone marrow function.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Baseline left ventricular ejection fraction (LVEF) ≥ 50%.
Exclusion Criteria:
* Concurrent anti-cancer treatment, or treatment with investigational therapy within 28 days prior to initiation of study treatment.
* Known active/untreated hepatitis B or C or chronic liver disease.
* Clinically significant cardiovascular disease or risk, including heart failure (New York Heart Association (NYHA) ≥ II), ischemic heart disease or recent coronary events/interventions, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, QT prolongation or risk of ventricular dysrhythmias, poorly controlled hypertension, peripheral arterial disease, dilated cardiomyopathy, or unstable angina.
* Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
* Concomitant use of any drug or herbal medicine known to strongly inhibit or induce CYP3A4 or CYP2C8 activity, oral coumarin-derivative anticoagulants.
Radiation Therapy Approaches for People With Prostate Cancer
This trial compares two radiation therapy approaches, HDR brachytherapy boost versus SBRT alone, for treating non-metastatic unfavorable intermediate-, high-, or very high-risk prostate cancer.
NCT07751159 · Phase 2 · Memorial Sloan Kettering Cancer Center
Recruiting sites: New Jersey, New York
Read full eligibility criteria
Inclusion Criteria:
* Non-metastatic prostate cancer.
* Classified as unfavorable intermediate-, high-, or very high-risk prostate cancer according to NCCN risk stratification guidelines. (Note: cT3a or T3b by MRI or PSMA PET allowed)
* Considered by the treating radiation oncologist as a suitable candidate for both HDR brachytherapy boost and SBRT
Exclusion Criteria:
* None
Sitagliptin With Pembro in RCC and Melanoma
This phase 1 trial combines sitagliptin, an oral DPP-4 inhibitor, with pembrolizumab, a PD-1 checkpoint inhibitor, in patients with advanced renal cell carcinoma or advanced melanoma whose disease has progressed on prior anti-PD-1/PD-L1 therapy.
NCT07634380 · Phase 1 · Fernando Maciel Barbosa
Recruiting sites: Iowa
Read full eligibility criteria
INCLUSION CRITERIA
1. Histologically and/or cytologically confirmed unresectable metastatic renal cell carcinoma with clear cell component with no neuroendocrine differentiation component) or unresectable metastatic melanoma (excluding uveal or mucosal melanoma) that have progressed on treatment with an anti-PD-1/PD-L1 mAb administered either as a monotherapy, or in combination with other immune checkpoint inhibitors or other therapies. Progression on treatment with an anti-PD-1/PD-L1 mAb is defined by meeting all of the following criteria:
1. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb
2. Has demonstrated disease progression after anti-PD-1/PD-L1 mAb as defined by RECIST v1.1. The initial evidence of disease progression (PD) is confirmed by a second assessment no less than 4 weeks from the date of the first documented PD
3. Progressive disease has been documented within 12 weeks from last dose of anti-PD-1/PD-L1 mAb (refractory disease) or ≥12 weeks from last dose of anti-PD-1/PD-L1 mAb (late relapse)
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
3. Measurable disease meeting the following criteria:
1. At least 1 lesion of ≥10mm in the longest diameter for a non-lymph node or ≥15mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using computerized tomography/magnetic resonance imaging (CT/MRI)
2. Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion
4. Aged 18 years and older
5. The participant is capable of understanding and complying with the protocol requirements and has signed the informed consent document
6. Participants must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy to \< Grade 1 CTCAE unless clinically insignificant and/or stable on supportive therapy.
7. No active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
8. Women of childbearing potential (WOCBP) - defined as females who have experienced menarche, have not undergone permanent surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), and are not postmenopausal (no menses for ≥12 consecutive months without an alternative medical cause) - must meet all of the following criteria:
1. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test must be performed and must be negative prior to enrollment.
2. Agree to use at least one highly effective method of contraception during the study and for a minimum of 4 months after the last dose of pembrolizumab.
Acceptable highly effective methods include:
* Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, or transdermal)
* Progestogen-only hormonal contraception (oral, injectable, or implantable)
* Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
* Bilateral tubal occlusion
* Vasectomized partner (if confirmed as the sole sexual partner)
* Complete sexual abstinence (only if this is the participant's usual and preferred lifestyle)
9. Male participants must:
* Use a condom with spermicide during the study and for at least 4 months after the last dose of pembrolizumab, and
* Ensure that their female partners of childbearing potential use an additional highly effective method of contraception during this period.
10. Able to swallow pills
11. Adequate archival tissue sample ( 5-10 slides at 5µm) of at least one tumor lesion is mandatory. If archival tissue is not available, Participant must agree to a new biopsy sample.
EXCLUSION CRITERIA
A patient meeting any of the following criteria is not eligible to participate in this study:
1. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
2. Participants with renal cell carcinoma with histologic/cytologic component of neuroendocrine differentiation
3. Participants with uveal or mucosal melanoma
4. Participants with both renal cell carcinoma and melanoma
5. Participants with diabetes mellitus requiring insulin therapy or sulfonylurea
6. Participants taking oral antihyperglycemics (e.g., metformin, DPP-4 inhibitor, SGLT-2 inhibitor) for any cause within 3 months of starting study drug
7. Participants with documented history of hypoglycemia requiring medical intervention, oral or intravenous carbohydrate ( glucose, dextrose, fruit juice, or any form of glucagon) or who in the opinion of the investigator are not suitable to receive sitagliptin
8. Taking digoxin within 6 months of starting study drug
9. Known intolerance or history of severe hypersensitivity reaction (such as anaphylactic shock or angioedema) to sitagliptin or monoclonal antibody
10. Prior anticancer treatment within 28 days (or 5 times the half-life, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study treatment.
11. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of sitagliptin
12. Active uncontrolled infection requiring systemic therapy.
13. Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
14. History of organ allograft (participant has had an allogenic tissue/solid organ transplant)
15. Biologic response modifiers (e.g., granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before the first dose of study treatment
16. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical study
17. Females who are pregnant or breastfeeding
18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5mg/d of prednisone or equivalent) may be approved after consultation with the sponsor
19. Has history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
20. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
Strategic Endocrine Therapy and Targeted Radiotherapy for Prostate Cancer
This trial compares 6 months versus 18 months of androgen deprivation therapy (with an androgen receptor pathway inhibitor if indicated) combined with definitive external beam radiotherapy in patients with high-risk localized prostate adenocarcinoma.
NCT07364071 · Phase 2 · University of California, San Diego
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed adenocarcinoma of the prostate.
2. High-risk localized prostate cancer, defined as ≥1 of the following (per National Comprehensive Cancer Network or D'Amico criteria):
1. Prostate specific antigen ≥ 20 ng/mL
2. Gleason score 8-10
3. Clinical stage T3a or higher; imaging can be used to determine T stage if there is macroscopic (gross) extraprostatic extension or invasion of the seminal vesicles or other non-prostate organs
3. No evidence of distant metastasis, confirmed by:
a. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) or equivalent staging imaging
4. Planning to receive definitive external beam radiotherapy and hormone therapy as standard of care (on label or medically accepted) treatment
5. Eastern Cooperative Oncology Group performance status 0-1.
6. Age ≥ 18 years.
7. Willingness to use adequate contraception if sexually active and of reproductive potential
8. Ability to understand and willingness to sign informed consent.
9. Stated willingness to comply with all study procedures and availability for the duration of the study.
Exclusion Criteria:
1. Evidence of metastatic disease, including nodal disease beyond the pelvis or distant metastases on imaging.
2. Clear evidence of regional nodal disease on conventional imaging.
3. Prior prostatectomy.
4. Prior systemic therapy for prostate cancer, including:
1. Androgen deprivation therapy (Note that participants who have started Androgen deprivation therapy within 90 days prior to randomization can be enrolled.)
2. Androgen receptor pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide, darolutamide).
3. Chemotherapy for prostate cancer.
5. Prior pelvic radiotherapy.
6. Any condition that, in the investigator's judgment, would compromise the patient's safety or compliance.
Study Investigating Intravesical HDAC Inhibition to Improve Response to Immuno-Oncology Agents
This trial studies neoadjuvant intravesical romidepsin (an HDAC inhibitor) combined with intravenous durvalumab (an immune checkpoint inhibitor) in cisplatin-ineligible patients with muscle-invasive bladder cancer prior to definitive local therapy.
NCT06963346 · Phase 1 · H. Lee Moffitt Cancer Center and Research Institute
Recruiting sites: Florida
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically confirmed MIBC (T2-T4a, N0, M0 per American Joint Commission on Cancer \[AJCC\]) pure or mixed histology urothelial carcinoma.
* Patients must be ineligible for cisplatin-based chemotherapy due to any of the following: Creatinine clearance (CrCl) \< 60 mL/min by the Cockcroft-Gault formula; Hearing impaired ≥ Grade 2 by CTCAE criteria; Neuropathy ≥ Grade 2 by CTCAE criteria; Heart failure NYHA ≥ III; ECOG ≥ 2.
* Patients must be medically fit for TURBT and radical cystectomy (RC
* Age ≥ 18 years
* Body weight \>30 kg
* Ability to understand and willingness to sign IRB-approved informed consent.
* Willing to provide tumor tissue, blood, and urine samples for research.
* ECOG performance status 0 or 1 (Karnofsky ≥80%).
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants must have adequate organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1500/mcL; Platelet count ≥100,000/mcL; Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN); total bilirubin must be \< 3 x ULN for patients with Gilberts syndrome; AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal; Measured creatinine CL \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
* Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥120 days after the last dose of durvalumab.
* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* Patient must have a life expectancy of at least 12 weeks
Exclusion Criteria:
* Patients with active or prior documented autoimmune disease within the past 2 years prior to Screening or other immunosuppressive agent within 14 days of study treatment. NOTE: Patients with well controlled type 1 diabetes mellitus, vitiligo, Graves' disease, Hashimoto's disease, eczema, lichen simplex chronicus, or psoriasis not requiring systemic treatment (within the past 2 years prior to Screening) are not excluded.
* Patients who have concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma. Patients with history of non-invasive (Ta, T1, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.
* Patients who have another malignancy that could interfere with the evaluation of safety or efficacy of the study drugs. Patients with a prior malignancy will be allowed without Principal Investigator approval in the following circumstances: Not currently active and diagnosed at least 5 years prior to the date of registration; Non-invasive diseases such as low risk cervical cancer or any cancer in situ; Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy), and in which no chemotherapy was indicated (e.g. low/intermediate risk prostate cancer, etc.). Patients with other malignancies not meeting these criteria must be discussed prior to registration.
* Patients who have received any prior immune checkpoint inhibitor (i.e. anti-KIR, anti-PD-1, anti- PD-L1, (including durvalumab) anti-CTLA4 or other).
* Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury or specific anti-cancer treatment ≤ 4 weeks prior to starting study drug, or patients who have had placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
* Patients who have clinically significant cardiac diseases deemed not fit for radical cystectomy, including any of the following: History or presence of serious uncontrolled ventricular arrhythmias; Clinically significant resting bradycardia; Any of the following within 3 months prior to starting study drug: severe/unstable angina, Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA); Uncontrolled hypertension defined by a SBP ≥ 180 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
* Patients who have history of chronic active liver disease or evidence of acute or chronic Hepatitis B Virus (HBV) or Hepatitis C (HCV).
* Patients who have known diagnosis of human immunodeficiency virus (HIV) infection. Testing is not required in absence of clinical suspicion.
* Patients who have known diagnosis of any condition (e.g. post-hematopoietic or solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy which cannot be stopped for the duration of the clinical trial. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
* Patients with any serious and/or uncontrolled concurrent medical conditions.
* Patients who have used any live viral vaccine for prevention of infectious diseases within 4 weeks prior to study drug(s). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. COVID vaccination is allowed.
* Patients unwilling or unable to comply with the protocol.
* Patients with a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
* Patients who participate in any other therapeutic clinical trials, including those with other investigational agents not included in this trial throughout the duration of this study.
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference.
* Patients with local symptoms from bladder cancer, (e.g. gross hematuria, dysuria, etc.) who are deemed to be unable to complete the treatment protocol per PI.
* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
Study of Oral MRT-2359 With Apalutamide in Prostate Cancer
MRT-2359, an investigational oral agent (mechanism not stated in registry), is being studied in combination with apalutamide in patients with castration-resistant prostate cancer who have progressed on prior ARPi therapy.
NCT07745361 · Phase 2 · Monte Rosa Therapeutics, Inc
Recruiting sites: California, Colorado, Kansas, Maryland, Michigan, Nebraska, New Jersey, North Carolina, Pennsylvania, Tennessee, Utah, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
* Age \> 18 years
* A predicted life expectancy of ≥ 3 months and an ECOG performance status ≤ 1
* Have histologically or cytologically confirmed castration-resistant adenocarcinoma of the prostate without small cell histology and with androgen receptor (AR) mutations
* Have not had prior treatment with more than 1 prior taxane-based chemotherapy regimen for castration-resistant prostate cancer
* Have no prior treatment with an AR degrader, opevesostat, or similar therapy
* Has ongoing (chemical or surgical) androgen deprivation with serum testosterone \< 50 ng/dL (\< 1.7 nM)
* Has received prior treatment with poly(ADP-ribose) polymerase (PARP) inhibitor, if appropriate, or deemed ineligible to receive treatment by the Investigator, or has refused PARP inhibitor treatment
* Has received prior treatment with at least 1 line of ARPi
* Have disease measurable per Prostate Cancer Working Group 4 (PCWG4) criteria, with or without measurable disease by RECIST 1.1
* Be able to provide a tumor biopsy for biomarker analysis during the Screening period
* Have adequate organ function
Exclusion Criteria:
* • Have received prior chemotherapy, definitive radiation, or biological cancer therapy within 21 days before the first dose of study treatment or have any AEs that have failed to recover to baseline
* Have received prior therapy with a GSPT1 degrader that was discontinued due to an AE
* Have received prior auto-HCT and have not fully recovered from effects of the last transplant
* Have received allogeneic hematopoietic stem cell transplantation within past 6 months and/or have symptoms of graft-versus-host disease
* Current use of chronic systemic steroid therapy in excess of replacement doses
* Have clinically active central nervous system involvement and/or carcinomatous meningitis
* Have a confirmed history of (noninfectious) pneumonitis that required steroids
* Clinically significant cardiac disease
Study to Assess the Efficacy and Safety of Rina-S With or Without Bevacizumab Compared to Investigator's Choice of Platinum-based Chemotherapy With or Without Bevacizumab as Second-line Treatment in Participants With Recurrent Platinum-sensitive Ovarian Cancer
Rina-S, a biological agent (mechanism/target not explicitly stated in the registry) given with or without bevacizumab, is compared to investigator's choice platinum-based chemotherapy with or without bevacizumab as second-line treatment for recurrent platinum-sensitive high-grade ovarian, primary peritoneal, or fallopian tube cancer.
NCT07564141 · Phase 3 · Genmab
Recruiting sites: California, Connecticut, Oregon, Pennsylvania, West Virginia, Wisconsin
Read full eligibility criteria
Key Inclusion Criteria:
* Participant must have histologically confirmed high-grade serous or endometrioid epithelial ovarian cancer (EOC), including primary peritoneal or fallopian tube cancer.
* Participant must have documented recurrence or progression after first-line (1L) platinum-based chemotherapy regimen (carboplatin + paclitaxel ≥ 4 cycles) with or without bevacizumab and have platinum-sensitive disease defined as radiographic progression at least 6 months (ie, \>183 days) after their last dose administration of platinum-based therapy.
* Prior poly (ADP-ribose) polymerase inhibitor(s) (PARPi) maintenance therapy (alone or in combination with bevacizumab) is required for participants with breast cancer susceptibility gene (BRCA 1- and BRCA 2)-mutated (germline or somatic) or homologous recombination deficiency (HRD)-positive disease.
* Participants must have measurable disease per RECIST v1.1 by investigator at baseline.
* All participants must provide a tumor specimen.
* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at baseline.
Key Exclusion Criteria:
* Participants with clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumors.
* Participant has received previous therapy with other anti-angiogenetic agents different from bevacizumab or biosimilar.
* Participant has received prior therapy with an antibody-drug conjugate (ADC) containing a topoisomerase-1 inhibitor.
* Participant has received prior therapy with an ADC targeting folate receptor alpha (FRα).
Note: Other protocol-defined Inclusion and Exclusion criteria may apply.
Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene
Phase I trial combining neratinib (a kinase inhibitor targeting HER2/EGFR family signaling) with trastuzumab deruxtecan (a HER2-directed antibody-drug conjugate delivering a topoisomerase I inhibitor payload) in patients with HER2-altered metastatic or unresectable solid tumors, including a dedicated cohort for HER2-positive metastatic/unresectable pancreatic adenocarcinoma.
NCT05372614 · Phase 1 · National Cancer Institute (NCI)
Recruiting sites: California, Florida, Illinois, Kentucky, Massachusetts, Missouri, Ohio, Pennsylvania, Texas, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically confirmed malignancy that is metastatic or unresectable with participation in this clinical trial determined to be the best option for next treatment in the opinion of the investigator, and meet the following specific criteria:
* Patients enrolling in Part 1 (Dose Escalation) may have a diagnosis of any solid tumor
* Patients enrolling in the Part 2 Pharmacodynamic Cohort may have a diagnosis of any solid tumor except pancreas cancer (NOTE: pancreatic cancer excluded from this cohort after Revision 11 activation due to the addition of the pancreatic specific cohort)
* Patients enrolling in the Part 2 Pancreatic Cohort must have a diagnosis of pancreatic adenocarcinoma (PDAC) and meet the HER2 positivity guidance
* Patients must have a solid tumor with HER2-positivity as determined by any one or more of the following:
* HER2 overexpression defined by immunohistochemistry (IHC) 3+
* ERBB2 amplification by in situ hybridization (ISH) or next-generation sequencing as determined by any Clinical Laboratory Improvement Act (CLIA) certified lab
* A known HER2 activating mutation
* HER2 overexpression by IHC/ISH will follow histology specific American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines for breast and gastric cancers. HER2 overexpression by IHC/ISH for the Pancreatic Cohort will follow ASCO-CAP guidelines for gastric cancers. For tumor histologies without specific guidelines the following criteria will apply:
* HER2 IHC should be performed first, followed by ISH methods in cases showing 2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or 1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals per cell are considered positive by ISH
* Known HER2 activating mutations:
* G309A/E
* S310F/Y
* S653C
* V659E
* G660D
* R678Q
* E693K
* Q709L
* L755S/P
* Del. 755-759
* D769Y/H
* G776V/C
* V777L
* V842I
* T862A
* L869R
* H878Y
* All exon 20 insertions, including:
* A771\_Y772insYVMA
* A775\_G776insYVMA
* Y772\_A775dup
* P780\_Y781insGSP
* G778\_P780dup
* V697L
* T733I
* D769N
* L841V
* L866M
* R896C
* If a different mutation is identified, contact the study chair for conferral. Synonymous mutations are not eligible
* Patients must have received at least 1 prior line of therapy in the advanced/metastatic setting. No limitation on number of prior therapies; however, patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab, TDM-1, lapatinib, etc.)
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of neratinib in combination with DS-8201a in patients \< 18 years of age, children are excluded from this study
* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* Hemoglobin \>= 9.0 g/dL (\>= 8.0 g/dL for gastric cancer \[GC\] only) (within 14 days of enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Leukocytes \>= 3.0 K/cumm (within 14 days of enrollment)
* Absolute neutrophil count \>= 1.5 K/cumm (within 14 days of enrollment)
* No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
* Platelets \>= 100 K/cumm (within 14 days of enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Serum albumin \>= 2.5 g/dL (within 14 days of enrollment)
* Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN), (\< 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14 days of enrollment)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (if liver metastases are present =\< 5 x ULN) (within 14 days of enrollment)
* International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\< 1.5 x institutional ULN (within 14 days of enrollment)
* This applies only to patients who are not receiving therapeutic anticoagulation that may affect INR. Those who are on therapeutic anticoagulation, should be on a stable dose for 4 weeks and should be considered within therapeutic range
* Creatinine =\< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
* Patients who are human immunodeficiency virus (HIV)-positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
* They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/ul over the past 2 years, unless it was deemed related to THE CANCER AND/OR CHEMOTHERAPY-induced bone marrow suppression
* For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/ul during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
* They must have an undetectable viral load and a CD4 count \>= 250 cells/uL within 7 days of enrollment
* They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose \> 4 weeks
* Patients with radiographically new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible only if has no progressive clinical symptoms and if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients should be New York Heart Association functional classification of class 2B or better
* Patients must have left ventricular ejection fraction (LVEF) \>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization/enrollment
* Part 2, Pancreatic cohort ONLY: Patients must have disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Part 2, PD cohort ONLY: Patients must have disease that is evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Part 2, PD cohort ONLY: Patients must have at least one lesion suitable for biopsy without significant risk to the patient. The biopsiable lesion can be the same as the evaluable lesion for response by RECIST 1.1
* HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic; thus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 1 month after the last dose of neratinib, or at least 7 months after the last dose of DS-8201a, whichever is longer (women of childbearing potential \[WOCBP\] only). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after the last dose of neratinib, or 4 months after completion of DS-8021a administration, whichever is longer
* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study
* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* With the exception of medications that are under investigation in the study (e.g., standard of care, comparators, or combination therapies), the following medications, treatment, and procedures will be prohibited during the treatment period:
* Other anticancer therapy, including small-molecule targeted agents within 2 weeks or five half-lives, whichever is longer; chemotherapy otherwise not specified (including, but not limited to cytotoxic chemotherapy, antibody drug conjugates, retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal antibody within 4 weeks; and nitrosoureas or mitomycin C within 6 weeks (concurrent use of hormones for noncancer-related conditions \[e.g., insulin for diabetes and hormone replacement therapy\] is acceptable)
* Other investigational therapeutic agents
* Patients who have had major surgery or radiation within 4 weeks; palliative stereotactic radiation within 2 weeks (except for palliative radiation to known metastatic sites as long as it does not affect assessment of response or interrupt treatment for more than the maximum time specified in dose modification section)
* Radiotherapy to the thorax (palliative radiation to known metastatic sites in the thoracic spine is permitted in this study)
* Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra-articular steroid injections are permitted in this study); chronic replacement dose steroids (e.g., for those with adrenal insufficiency) are permitted in this study
* Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
* Concomitant treatment with chloroquine or hydroxychloroquine is not allowed during the study treatment due to concern for overlapping toxicities. If treatment with chloroquine and hydroxychloroquine treatment is absolutely required, study treatment must be interrupted. If chloroquine or hydroxychloroquine is administered, then a wash-out period of more than 14 days is required before restarting study treatment
* Receipt of live, attenuated vaccine (messenger ribonucleic acid \[mRNA\] and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug
* Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
* Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, or neratinib
* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
* Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant use with proton pump inhibitors and P-glycoprotein substrates. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Patients with a medical history of myocardial infarction within 6 months before enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association class II to IV)
* Patients with a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
* Patients with clinically significant corneal disease in the opinion of the investigator
* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment) (GC indication)
* Patients with spinal cord compression
* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade =\< 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy)
* Patients with substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
* Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to other agents used in this study
* Prior treatment with neratinib or DS-8201a
* Clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; grade 2 (G2) or greater diarrhea at baseline. Please contact the study principal investigator (PI) for any patient with more than two episodes of diarrhea per day averaged over at least a 7 day period at time of screening to determine whether the diarrhea would be considered clinically significant
* Inability to swallow tablets
* Patients with active additional malignancy or a personal history of additional malignancy that may affect outcome of disease under treatment (patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen at the discretion of the treating investigator are allowed)
* Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation
A Study Comparing Two Immunotherapy Options for Human Papillomavirus Positive HPV-Positive Head and Neck Cancer After Treatment
This trial compares the immunotherapy combination of cemiplimab plus fianlimab versus cemiplimab alone (mechanisms/targets not further specified in the registry) as treatment in adults with HPV-positive oropharyngeal head and neck cancer who have detectable minimal residual disease after completing curative-intent therapy.
NCT07179315 · Phase 2 · University of Chicago
Recruiting sites: Illinois
Read full eligibility criteria
Inclusion Criteria:
* Patients must have history of histologically confirmed squamous cell carcinoma of the oropharynx.
* Must be HPV positive; testing must be compliant with meeting any one or more of the following criteria:
* p16 IHC positivity (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al.37).
* HPV PCR positivity.
* HPV in situ hybridization (ISH) positivity.
* Completed curative intent therapy. Acceptable curative intent therapies may include any combination of surgery, radiotherapy, and/or chemotherapy is eligible. Curative intent therapy must be completed at least 1 month prior to enrollment.
* Any T or N stage at time of initial diagnosis is permitted, including patients with unknown primary, supraclavicular or mediastinal nodal involvement at the time of curative intent treatment.
* Detectable ctHPVDNA in plasma confirmed by NavDx prior to enrollment based on the clinically validated circulating tumor-tissue-modified HPV (TTMV®) DNA plasma assay. Patients with detectable ctHPVDNA in plasma from other commercially available CLIA-certified assays are also eligible, however a positive NavDx assay is required and will be obtained during screening.
* PD-L1 biomarker analysis from a core or excisional biopsy must be performed by IHC using the 22C3 antibody and a CPS score must be calculated for stratification. If unavailable, result from a fine-needle aspirate can also be acceptable. Local testing is acceptable.
* No definitive clinical or radiographic evidence of disease evaluated by clinical examination and cross-sectional imaging and/or PET imaging prior to randomization. Patients with equivocal results on imaging are eligible.
* Patients must be willing and able to provide written informed consent for the trial.
* Patients must be at least 18 years of age on day of signing informed consent.
* Have a performance status of 0 or 1 on the ECOG Performance Scale. An ECOG performance status of 2 is acceptable if the patient was ECOG 0/1 prior to curative intent therapy and is in the midst of recovery from curative intent therapy.
* Demonstrate reasonable organ function as defined below in Table below
* System and Laboratory Value
* Hematological
* Absolute neutrophil count (ANC): ≥1,500 /mcL
* Platelets: ≥100,000 / mcL
* Hemoglobin: ≥9 g/dL
* Renal
\- Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤2.0 X upper limit of normal (ULN) OR ≥30 mL/min for subject with creatinine levels \> 2.0 X institutional ULN
* Hepatic
* Serum total bilirubin: ≤ 3 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 2 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
* WOCBP must have a negative serum (beta-hCG) at screening.
* WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy.
* Male study participants with WOCBP partners are required to use condoms during the study and until 6 months after the last dose of study treatment unless they are vasectomized or practice sexual abstinence.
* Vasectomized partner or vasectomized study participant must have received medical assessment of the surgical success.
* Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and LAM are not acceptable methods of contraception. Female condom and male condom should not be used together.
* WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment.
* All men must agree not to donate sperm during the trial and for 6 months after receiving the last therapy dose.
Exclusion Criteria:
* Clinical or radiographic evidence of gross disease that warrants further curative intent therapy or systemic/palliative therapy (e.g. platinum containing chemotherapy, cetuximab, pembrolizumab).
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10mg of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
* Note: Subjects with ≤ Grade 2 neuropathy or typical side effects from radiotherapy are an exception to this criterion and may qualify for the study.
* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
* Patients who are receiving any other investigational agents.
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
* Exclusions related to infection or immunodeficiency
* History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
* Active infection requiring therapy.
* Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
* Uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.
* Notes:
* Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
* Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
* Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
* Patients with HIV or hepatitis must be reviewed by a qualified specialist (eg, infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial
* Known hypersensitivity to the active substances or to any of the excipients.
* Received a live vaccine within 30 days of planned start of study medication.
o Live or live attenuated vaccination with replicating potential. If a patient intends to receive a COVID-19 vaccine before the start of study drug, participation in the study should be delayed at least 1 week after any COVID-19 vaccination. During the treatment period, it is recommended to delay COVID-19 vaccination until patients are receiving and tolerating a steady dose of study drug. A vaccine dose should not be less than 48 hours before or after study drug dosing.
* Has known history of, or any evidence of active, non-infectious pneumonitis.
* Exclusions related to cardiac conditions:
* Participants with a history of myocarditis.
* TnT or troponin I TnI \> 2x institutional ULN at baseline.
* Patients with TnT or TnI levels between \> 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are \> 1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include:
* Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
* Intrauterine device; intrauterine hormone-releasing system;
* Bilateral tubal occlusion/ligation;
* Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or
* Sexual abstinence
A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults With Advanced or Metastatic Solid Tumors
SHY-ONC6, an oral small-molecule proteasome inhibitor targeting the 19S proteasome regulatory particle ATPases, is being studied in a first-in-human phase 1 dose escalation/expansion trial in patients with advanced or metastatic solid tumors (including breast, colon, gastric, HCC, NSCLC, mesothelioma, pancreatic, prostate, and sarcoma) who have progressed on standard therapies.
NCT07705334 · Phase 1 · SHY Therapeutics
Recruiting sites: Arizona, Texas
Read full eligibility criteria
Inclusion Criteria:
* Male or female ≥18 years of age.
* Life expectancy \>3 months.
* ECOG performance status 0-1.
* Histologically/cytologically confirmed advanced or metastatic solid tumors that have progressed on or are intolerant/unsuitable for standard therapies. Eligible tumor types: TNBC, HR+ breast cancer, colon cancer, gastric cancer, HCC, NSCLC (adeno and squamous), mesothelioma, pancreatic cancer, HRPC, soft tissue sarcoma; other tumor types after Medical Monitor discussion. Stable CNS metastases ≥4 weeks post-radiotherapy and off steroids ≥14 days are permitted.
* ≥1 measurable lesion per RECIST v1.1 (prostate cancer with bone-only disease and elevated PSA assessed by PCWG3).
* Accessible tumor for biopsy
* Adequate organ/bone marrow function.
* Willingness and ability to provide informed consent.
* Negative serum pregnancy test and use of effective contraception through 90 days after last dose for women of childbearing potential.
* Male participants must use barrier contraception or abstinence and not donate sperm through 90 days after last dose.
Exclusion Criteria:
* High-risk cardiovascular disease.
* Concurrent anti-cancer treatment.
* Active infection requiring systemic treatment within 2 weeks pre-dose.
* History of another malignancy (with standard exceptions for in situ disease, non-melanoma skin cancers, and remission ≥2 years).
* Active HBV (HBV-DNA \>ULN), HCV (HCV-RNA \>ULN), or HIV (well-controlled HIV with CD4 ≥350 cells/µL and undetectable viral load permitted); AIDS-defining opportunistic infection within 12 months.
* Compromised pulmonary function within 6 months pre-dose .
* Pregnancy or breastfeeding.
* Recent radiotherapy, systemic anti-tumor therapy, other investigational therapy without appropriate washout.
* Major surgery ≤4 weeks pre-dose.
* Unable to swallow tablets or conditions affecting GI absorption.
* Any medical or psychiatric disorders affecting compliance and/or interpretation of study results.
* Persistent toxicities from prior anti-cancer therapy (exceptions apply)
* Clinically significant corneal disease.
* Unable to comply with prohibited concomitant medication restrictions.
DBC-664 in Adult Patients With Solid Tumors
DBC-664 is an intravenously administered biologic agent whose mechanism/target is not stated in the registry, being studied in a first-in-human Phase 1a/1b dose-escalation/expansion trial in patients with advanced/metastatic solid tumors including germ cell, lung, gastric/esophageal, urothelial, endometrial, and ovarian cancers.
NCT07705035 · Phase 1 · Duboce Biopharmaceuticals, Inc.
Recruiting sites: Colorado, Michigan, New Jersey, New York, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria:
* Must be ≥18 years of age at the time consent is signed.
* Has a histologically or cytologically confirmed unresectable recurrent locally advanced or metastatic solid tumor
* Has measurable disease per RECIST v1.1 (or mRECIST 1.1 for patients with pleural mesothelioma), as assessed by the local site Investigator/radiology.
Exclusion Criteria:
* Has a diagnosis of immunodeficiency.
* Has had a prior stem cell, bone marrow, or organ transplant.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has active or chronic hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
* Has an active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* Has a history of (noninfectious) pneumonitis that required steroids or current active pneumonitis/interstitial lung disease.
* Has symptomatic visceral spread of disease that poses a risk of life-threatening complications in the short term, per Investigator's opinion (including massive uncontrolled effusions \[pleural, pericardial, peritoneal\], pulmonary lymphangitis, and over 50% liver involvement).
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals with previously treated CNS metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 2 weeks by repeat imaging \[note that the repeat imaging should be performed during study Screening\]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* Has a history of a previous secondary malignancy within 3 years of Screening (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative therapy or other localized, low-grade tumors deemed cured, or whose natural history does not have the potential to interfere with the safety or efficacy assessments of the current study and not treated with systemic anticancer therapy \[except hormonal therapy\]).
* Has a known psychiatric or substance abuse disorder that would interfere with the individuals' ability to cooperate with the requirements of the study.
Intratumoral N17350 in Advanced Solid Tumors
N17350, a recombinant mutant porcine pancreatic elastase targeting the neutrophil elastase (ELANE) pathway given by intratumoral injection, is being studied as a treatment in adults with advanced solid tumors including breast, cutaneous squamous cell, melanoma, head and neck, and non-small-cell lung cancers.
NCT07339176 · Phase 1/2 · Onchilles Pharma Inc
Recruiting sites: California, New York, Texas
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥18 years (or legal age of consent in the study jurisdiction).
2. Able to provide written informed consent and willing/able to comply with study procedures, visits, and follow-up.
3. Advanced solid tumor malignancy (excluding lymphoma and other hematologic malignancies), with disease that has progressed on, is intolerant of, or is ineligible for standard therapies known to provide clinical benefit, or for whom no standard therapy is available.
4. ECOG performance status 0-1.
5. Measurable disease per IT-RECIST (Parts A1/A2) and RECIST v1.1 (Part A3), as applicable.
6. At least one injectable tumor lesion, meeting superficial or visceral criteria and deemed safe/accessible for injection:
1. Superficial lesions: ≥10 mm in longest diameter (or multiple lesions each ≥5 mm with aggregate longest diameter ≥10 mm), and ≤80 mm, accessible for direct injection (± ultrasound guidance).
2. Visceral lesions: ≥10 mm and ≤50 mm in longest diameter, accessible for direct injection.
3. Injected lesions must not involve/encase major blood vessels or otherwise pose an unacceptable bleeding/vascular risk, per investigator assessment and imaging review (as applicable).
4. Expansion (Part A3): at least 1 measurable lesion and at least 1 additional injectable lesion suitable for injection.
7. Adequate recovery from prior therapy: toxicities from prior anticancer treatment resolved to Grade ≤1 or baseline (except alopecia, controlled endocrine toxicities, or other stable toxicities as allowed per protocol/sponsor).
8. Adequate organ function, including hepatic, renal, and coagulation parameters per protocol-defined thresholds.
9. Adequate bone marrow function without transfusion support within 7 days prior to enrollment, per protocol-defined thresholds.
10. Tumor tissue requirements: willingness to provide a pre-treatment tumor biopsy and on-study post-treatment biopsy, if an accessible lesion is available and safe for biopsy, and biopsy does not interfere with injection/response assessment; and/or availability of archival tumor tissue (obtained within 2 years prior to treatment), per protocol.
11. Contraception requirements: participants of reproductive potential agree to use effective contraception and avoid pregnancy/fathering children from screening through 30 days after last dose; women of childbearing potential must have a negative pregnancy test within 14 days prior to first dose, per protocol.
Exclusion Criteria:
1. Serious psychiatric, medical, or other condition that would interfere with study participation or protocol procedures, in the investigator's judgment.
2. History of solid organ transplant.
3. Alpha-1 antitrypsin deficiency.
4. Hereditary or acquired bleeding disorder/coagulation factor deficiency.
5. Active autoimmune disease requiring systemic treatment within the past 6 months, except clinically stable autoimmune conditions in remission not requiring systemic therapy (per protocol).
6. Baseline QTcF \>480 ms.
7. Pregnant or breastfeeding.
8. Prior severe immune-mediated adverse event (imAE) from immunotherapy: ≥Grade 3 imAE within the past 16 weeks, any Grade 4 life-threatening imAE, or any neurologic/ocular AE of any grade (except controlled endocrine AEs on stable replacement therapy per protocol).
9. Another active malignancy (current or within the past 2 years) other than the disease under study, except specified low-risk cancers treated with curative intent or under active surveillance (per protocol).
10. Recent anticancer therapy: receipt of systemic anticancer therapy (including investigational agents) within 2 weeks prior to first dose (or 4 weeks for monoclonal antibodies/ADCs/other long half-life biologics), or within 5 half-lives, whichever is shorter.
11. Recent radiotherapy within 2 weeks prior to first dose.
12. Unresolved toxicity from prior anticancer therapy to \>Grade 1 or not at baseline (except Grade ≤2 neuropathy and other allowed exceptions per protocol).
13. Uncontrolled or unstable brain metastases (eligible only if neurologically stable for ≥4 weeks, and off steroids or on stable/decreasing steroids ≤10 mg/day prednisone equivalent; carcinomatous meningitis excluded).
14. Active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose.
15. Chronic viral infections not meeting protocol criteria:
1. HBV with detectable DNA unless on appropriate antiviral therapy
2. Active HCV with detectable HCV RNA (treated HCV permitted if RNA undetectable)
3. HIV infection with CD4+ count \<300/μL, detectable viral load, or HIV-related illness within 6 months
16. Use of systemic anticoagulants (e.g., warfarin, LMWH, DOACs) within 14 days prior to first dose.
17. Chronic systemic corticosteroids \>10 mg/day prednisone equivalent, or systemic immunosuppressive/anti-inflammatory medications within 4 weeks prior to first dose, except permitted topical/inhaled/local formulations or short courses for premedication per protocol.
18. Known allergy/hypersensitivity to N17350 or any excipients.
Ivonescimab Alone And With Carboplatin/Pemetrexed For NSCLC
Ivonescimab, a bispecific antibody targeting both PD-1 and VEGF-A, is studied alone or with carboplatin/pemetrexed chemotherapy in advanced non-squamous NSCLC harboring actionable genomic alterations (EGFR, ALK, ROS1, RET, or NTRK1-3) in patients previously treated with genotype-specific TKIs.
NCT07405190 · Phase 2 · Massachusetts General Hospital
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed advanced or metastatic non-squamous NSCLC not amenable to curative resection or radiation.
* AGA requirements as follows:
Ivonescimab monotherapy: Tumor harboring classical EGFR sensitizing mutation (i.e., L858R, exon 19 deletion), or ALK, ROS1, RET, or NTRK1-3 fusion, per local testing. Note: The number of patients with EGFR mutation-positive NSCLC enrolled will be capped at maximum of 10 (in order to ensure the assessment of non-EGFR disease subsets). Ivonescimab plus carboplatin/pemetrexed: Tumor harboring ALK, ROS1, RET, or NTRK1-3 fusion, per local testing.
* Prior therapy requirements as follows:
a. Prior genotype-specific standard-of-care targeted therapy must have included at least one genotype-appropriate TKI(s) specified below: i. EGFR sensitizing mutation: a third-generation EGFR TKI such as osimertinib or lazertinib ii. ALK fusion: a third- or fourth-generation ALK TKI such as lorlatinib or neladalkib (NVL-655) iii. ROS1 fusion: crizotinib, entrectinib, repotrectinib, or taletrectinib iv. RET fusion: selpercatinib or pralsetinib v. NTRK1-3 fusion: entrectinib, larotrectinib, or repotrectinib Ivonescimab monotherapy: Must have received platinum/pemetrexed chemotherapy. No limitations on the number of prior lines of systemic therapy including the number of lines of chemotherapy or TKI(s). Ivonescimab plus carboplatin/pemetrexed: May not have received any prior chemotherapy. No limitations on the number of prior TKI(s).
* At least 1 measurable lesion as assessed by investigator per the RECIST v1.1 criteria for both cohorts.
* Participants must be willing to undergo the mandatory pre-treatment and post-progression tissue biopsies. If archival pre-treatment tissue is available from within 6 months of study enrollment, with no new intervening systemic therapy since the biopsy, a repeat pre-treatment biopsy may be omitted upon discussion with the principal investigator. On-treatment tissue biopsy (obtained within 7 days prior to Cycle 2 Day 1) will be mandatory for patients in Cohort 1 and optional for patients in Cohort 2. In select cases, if medically deemed unsafe/not feasible, exception may be granted upon discussion with the principal investigator.
* Clinically asymptomatic treated or untreated brain metastases are allowed if they have not required increasing doses of steroids within 2 weeks prior to study entry for CNS symptoms.
* Age ≥18 years old.
* ECOG performance status of 0 or 1.
* Adequate Organ Function:
a. Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening CBC): i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L ii. Platelet count ≥ 100 × 109/L iii. Hemoglobin ≥ 9.0 g/dL b. Kidneys: i. Creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula (Cohorts 1 and 2) or estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min (for Cohort 1) or ≥30 mL/min (for Cohort 2) using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) ii. Urine protein \< 2+ or 24 hour urine protein quantification \< 1.0 g c. Liver: i. Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
* 2.5 × ULN; for patients with liver metastases, AST and ALT ≤ 5 × ULN d. Coagulation: prothrombin time (PT) or international normalized ratio (INR)
* 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose for at least one month prior to study enrollment.
* Female patients of childbearing age must have negative serum pregnancy test results before first ivonescimab drug dose or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
* Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab and until 6 months after the last doses of carboplatin and pemetrexed.
* Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab and until 90 days after the last doses of carboplatin and pemetrexed. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab and until 90 days after the last doses of carboplatin and pemetrexed.
Exclusion Criteria:
* Participants previously treated with immune checkpoint inhibitors or other T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents.
* Major surgical procedures or serious trauma within 4 weeks prior to first ivonescimab dose or plans for major surgical procedures within 4 weeks after the first ivonescimab dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to first ivonescimab dose.
* History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to first ivonescimab dose, including but not limited to:
1. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots). Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
2. Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
3. Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to first ivonescimab dose is not allowed; stability of anti-coagulation dosing will be defined by remaining on the same dose for at least one month prior to study enrollment.
4. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution.
* Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
* Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to first ivonescimab dose; however, the following will be allowed:
1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
2. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted.
* History of major diseases before first ivonescimab dose, specifically:
1. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 6 months prior to first ivonescimab dose, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
2. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before first ivonescimab dose
3. History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 6.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to first ivonescimab dose
4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before first ivonescimab dose
5. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to first ivonescimab dose
* Imaging during the screening period shows that the patient has:
1. Radiologically documented evidence of major blood vessel invasion (central pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery, common carotid artery, subclavian artery, superior vena cava) or tumor invading organs (heart, trachea, esophagus, central bronchi \[not including segmental bronchi\]) or if there is a risk of esophagotracheal or esophagopleural fistula in the opinion of the investigator.
2. Radiographic evidence of major blood vessel encasement with narrowing of the vessel or intratumor lung cavitation or necrosis that the investigator determines will pose a significantly increased risk of bleeding.
* Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to first ivonescimab dose, potential need for CNS radiation within the first cycle, or leptomeningeal disease.
Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent).
* Live vaccine or live attenuated vaccine within 4 weeks prior to planned first ivonescimab dose, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted.
* Severe infection within 4 weeks prior to first ivonescimab dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to first ivonescimab dose (excluding antiviral therapy for hepatitis B or C)
* Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 6
* Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic Note: Patients managed with indwelling catheters (eg, PleurX) are allowed.
* Any evidence of current ILD or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring systemic corticosteroids
* Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Known history of human immunodeficiency virus (HIV) whose viral load is not controlled.
* Current use of systemic corticosteroids (\>10 mg daily prednisone or equivalent)
* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
* Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to first ivonescimab dose. All patients with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV RNA levels above the lower limit of detection) are excluded.
* Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies
* History or current evidence of any condition (medical \[including adverse events from prior anticancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the patient to participate, in the opinion of the treating investigator
* Patient is breastfeeding or plans to breastfeed during the study
NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial
177Lu rhPSMA-10.1, a PSMA-targeted radioligand therapy, given alone or with degarelix (androgen deprivation therapy) as neoadjuvant treatment prior to radical prostatectomy in patients with high-risk or very high-risk localized/locally advanced prostate cancer.
NCT06066437 · Phase 1/2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Men ≥18 years of age
2. Histologically documented prostatic adenocarcinoma with an NCCN risk group of high-risk or very high-risk. NCCN High Risk and Very High-Risk criteria shown below. (Network, N.C.C. (2021).
Prostate Cancer (Version 02.2021).
High Risk:
* Has no very-high-risk features and has exactly one high-risk feature:
* cT3a
* Grade Group 4 or Grade Group 5
* PSA \>20 ng/mL
Very high:
* Has at least one of the following:
* cT3b-cT4
* Primary Gleason pattern 5
* 2 or 3 high-risk features
* \>4 cores with Grade Group 4 or 5
3. Prostate biopsy within 90 days prior to randomization is allowed for entry requirements. Prostate biopsy must be reviewed at MD Anderson Cancer Center. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible
4. ECOG performance status (PS) grade 1
5. No evidence of metastatic disease or clinically positive lymph nodes as documented by technetium99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans. Imaging may be obtained up to 60 days prior to randomization
6. Minimum prostate tumor volume of 1.5 cm3 or greater as measured on prostate MRI within 60 days prior to randomization
7. Distant metastatic disease or clinically positive lymph nodes not identified by conventional imaging including by technetium-99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans but identified PSMA PET is allowed based on provider discretion
8. PSMA expression within the primary tumor with a minimum SUVmax of the primary tumor of at least 8
9. Localized or locally advanced disease deemed by the surgeon to be resectable. Patients must be appropriate candidates for and plan to undergo radical prostatectomy and pelvic lymph node dissection
10. No prior treatment for prostate cancer including prior surgery (excluding transurethral resection of the prostate \[TURP\]), cryoablation, pelvic lymph node dissection, radiation therapy, hormonal therapy or chemotherapy
11. Adequate bone marrow function documented by:
* Hemoglobin ≥11 g/dL
* Absolute neutrophil count ≥1.5 x 109/L
* Platelet count ≥150 x 109/L
12. Adequate renal function defined as creatinine \<1.5 x ULN or estimated glomerular filtration rate \>60 mL/min/1.73 m2 using BSA with CKD-EPI
13. Adequate hepatic function documented by:
* Total bilirubin ≤1.5 x ULN
* AST ≤2.5 x ULN
* ALT ≤2.5 x ULN
* Alkaline Phosphatase (ALP) ≤2.5 x ULN
Patients with Gilbert's syndrome do not need to meet total bilirubin requirements provided their total bilirubin is not greater than their historical level. Gilbert's syndrome must be documented appropriately as past medical history
14. Consents to providing whole blood samples for correlative PSMA evaluation of circulating tumor cells and extra cellular vesicles
15. Willing and able to comply with clinic visits and study-related procedures
16. Provide informed consent signed by study patient
17. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 6 months following the last dose of study drug. If the subject is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies and their partners. Donation of sperm is not allowed while on study drug and for 3 months following the last dose of study drug.
Exclusion Criteria:
1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-α reductase inhibitors allowed), or LHRH agonists/antagonists
2. Currently enrolled in another interventional study
3. Concurrent treatment with systemic corticosteroids (prednisone dose \>10 mg per day or equivalent) or other immunosuppressive drugs \<14 days prior to treatment initiation Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted.
4. Known evidence of an active infection requiring systemic therapy such as uncontrolled human immunodeficiency virus (HIV), active hepatitis, or fungal infection. Uncomplicated urinary tract infection (UTI) does not qualify as an excluding infection.
* Patients with HIV must be on an effective anti-retroviral regimen atleast four weeks prior to enrollment, HIV viral load less than 400 copies/mL and CD4+ T cell counts greater than 350 cell/uL.
* Patients with HIV must agree to adhere to anti-retroviral therapy for the entirety of their participation in the protocol unless dictated by treatment toxicities.
* Patients on Tenofovir will be excluded as there is a known risk of proximal renal tubule dysfunction leading to renal toxicity. Given that PSMA is expressed on the proximal tubule there is a theoretical risk of overlapping toxicity.
5. History of clinically significant cardiovascular disease including, but not limited to:
* Myocardial infarction or unstable angina ≤6 months prior to treatment initiation
* Clinically significant cardiac arrhythmia
* Deep vein thrombosis, pulmonary embolism, stroke ≤6 months prior to treatment initiation
* Congestive heart failure (New York Heart Association class III-IV)
* Pericarditis/clinically significant pericardial effusion
* Myocarditis
* Endocarditis
6. History of major implant(s) or device(s), including but not limited to:
* Prosthetic heart valve(s)
* Current or prior history of infection or other clinically significant adverse event associated with an exogenous implant or device that cannot be removed
7. Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) ≤2 years prior to enrollment
8. Has received major surgery within 90 days of first administration of study drug
9. Prior allogeneic stem cell transplantation or recipients of organ transplants or autologous stem cell transplantation at any time MD Anderson Protocol Number: 2022-0500 2022-0500 Version Date 8/29/2023 26
10. Any medical, psychological or social condition that in the opinion of the investigator, would preclude participation in this study
11. Previously received external beam irradiation to the pelvis or to a field that includes more than 30% of the bone marrow or kidneys
12. Previous treatment with any of the following: PSMA-targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
13. Transfusion of blood products for the sole purpose of meeting the eligibility criteria for this clinical trial
14. Patient has a functionally or anatomically solitary kidney.
15. Patients with Hydronephrosis and a Mag3 Lasix Renogram that demonstrates objective urinary obstruction.
PDT For Induction Therapy For Head And Neck Cancer
Toripalimab-tpzi, a PD-1-blocking monoclonal antibody, is being studied in combination with cisplatin and docetaxel as induction therapy for CPS-positive locally advanced head and neck squamous cell carcinoma.
NCT07214987 · Phase 2 · Massachusetts General Hospital
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
* Participants must have a new diagnosis of histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, sinonasal cavities or unknown primary HNSCC.
* Participants with HPV-independent SCC or HNSCC or other head and neck subsites must have stage III or non-metastatic stage IV at the time of diagnosis. Participants with HPV-associated oropharynx SCC must have stage II or stage III disease.
* Participants must be determined by the investigator to be candidates for induction systemic therapy due to reasons such as the extent of primary tumor at the time of diagnosis, rate of progression, symptom burden or potential benefit of cytoreduction prior to definitive local therapy.
* Age ≥18 years. Because no dosing or adverse event data are currently available on the use of toripalimab in combination with cisplatin and docetaxel in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
* ECOG performance status ≤ 1
* Life expectancy of greater than 12 weeks.
* Participants must meet the following organ and marrow function as defined below:
Hemoglobin ≥8.0 g/dL absolute neutrophil count ≥1500/mcL platelets ≥100,000/mcL total bilirubin ≤ 2 institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 2 × institutional ULN creatinine ≤ 2 x institutional ULN OR glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Because immunotherapy agents as well as cisplatin and docetaxel are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of toripalimab administration.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Diagnosis of EBV-associated nasopharynx squamous cell carcinoma
* Strong clinical suspicion or histologic confirmation of cutaneous squamous cell carcinoma
* Histology other than squamous cell carcinoma.
* Proven distant metastases (below the clavicle) by clinical or radiographic measures.
* Prior radiotherapy to the head and/or neck that excludes the patient from receiving curative-intent radiation to involved areas.
* Pre-existing peripheral neuropathy CTCAE grade 2 or higher
* Participants who are receiving any other investigational agents for this condition.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to toripalimab, cisplatin or docetaxel.
* An autoimmune condition requiring treatment with systemic corticosteroids within the past 30 days. Long-term steroid replacement for patients with adrenal insufficiency is allowed.
* Presence of a second malignancy that is considered active by the investigator. A second malignancy should be considered active if any one of the following are present: Administration of antineoplastic therapy for the second malignancy in the previous 6 months; Clinically significant radiographic changes in the prior 6 months that are attributed to the second malignancy; Concern by the investigator that the second malignancy may require antineoplastic treatment during the patient's treatment for their head and neck cancer or in the next 6 months, whichever timeframe is expected to be longer
* Participants receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
* Pregnant women are excluded from this study because toripalimab, cisplatin and docetaxel have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with toripalimab, cisplatin and docetaxel, breastfeeding should be discontinued if the mother is treated with toripalimab. These potential risks may also apply to other agents used in this study.
Phase 1 Study Of LNK001 In Advanced Or Metastatic Clear Cell Renal Cell Carcinoma
LNK001, an autologous logic-gated CAR T-cell therapy targeting CAIX and ENPP3, is being studied (with cyclophosphamide/fludarabine lymphodepletion) in previously treated advanced or metastatic clear cell renal cell carcinoma.
NCT07564232 · Phase 1 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Patients with histologically or cytologically confirmed metastatic/advanced RCC with a clear cell component who have received at least one prior line of systemic treatment in the advanced or metastatic setting, including at least one PD-1/PD-L1 immune checkpoint inhibitor (ICI) and one tyrosine kinase inhibitor (TKI). Patients with locally advanced disease who are eligible for curative resection are excluded.
• For patients who received one prior line of therapy, they must have had evidence of disease progression. For patients who received 2 or more prior lines of therapy, evidence of progression is not required if they stopped treatment for intolerance.
2. Confirmation of CAIX expression ≥ 50% at any intensity (greater than 0) by immunohistochemistry staining of the patient's primary renal tumor or a metastatic lesion biopsy specimen will be required for enrollment in the study. Both overall extent of expression and staining intensity will be scored. Archival tissues that exist prior to the time of enrollment will be used for this purpose.
3. Patients must have at least one measurable site of disease per RECIST version 1.1.4.
4. ECOG performance status ≤ 1.
5. Age ≥ 18 years.
6. Patients must have adequate organ and marrow function as defined below:
* Hemoglobin ≥ 8 g/dl
* Absolute neutrophil count ≥1,500/mcL
* Platelets ≥100,000/mcL
* Total bilirubin ≤ 1.5 mg/dL; for patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN
* AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN; for patients with liver metastases, AST and ALT ≤ 5 × ULN
* Creatinine (CrCl) ≥ 30 mL/min using either the Cockcroft-Gault formula or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
7. INR and PT ≤ 1.5 x ULN and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). Therapeutic anticoagulation with low molecular weight heparin (LMWH) or direct oral anticoagulant (DOAC) is permitted if the participant is on a stable therapeutic dose for at least 2 weeks at the time of enrollment.
8. Left ventricular ejection fraction ≥ 45% by echocardiogram or MUGA scan.
9. For patients with a history of chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections, the HBV and HCV viral loads must be undetectable.
10. Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy.
11. The effects of LNK001 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy)
* History of bilateral tubal ligation or another surgical sterilization procedure.
* Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) before study entry. Pregnancy test must be repeated on the day of first infusion, if test performed \> 14 days before starting study drug.
* Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the LNK001. Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of LNK001. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of LNK001.
Approved methods of birth control are as follows:
* Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring)
* Intrauterine device (IUD)
* Tubal Ligation or hysterectomy
* Subject/Partner post vasectomy
* Implantable or injectable contraceptives, and condoms plus spermicide
* Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control
12. Ability to understand and the willingness to sign a written informed consent document for the clinical trial.
13. Willingness to enroll in a 15-year long term follow-up surveillance protocol post LNK001 dosing.
Exclusion Criteria:
1. Participants must not have any other malignancies requiring active treatment within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, ductal carcinoma in situ of the breast or low-risk early-stage prostate adenocarcinoma with negligible risk of metastasis or death.
2. Major surgical procedures or serious trauma within 4 weeks prior to enrollment or plans for major surgical procedures within 4 weeks after cell infusion (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment.
3. History of major cardiovascular diseases prior to enrollment: unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 6 months prior to consenting, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia, clinically significant pericardial effusions).
4. Symptomatic CNS metastases, leptomeningeal disease, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrollment, or potential need for CNS radiation within the first 28 days from LNK001 therapy.
• Patients with treated/stable brain metastases are allowed on protocol if they had brain metastases that received CNS-directed therapy, such as surgery or treatment with radiosurgery or Gamma knife, without recurrence or edema for at least 1 month (4 weeks). Patients actively requiring glucocorticoids for uncontrolled brain or leptomeningeal metastases are not eligible. Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent).
5. Active autoimmune diseases requiring systemic therapy (e.g., with disease-modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy). However, the following will be allowed:
* Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
* Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections.
6. Ongoing treatment with systemic corticosteroid therapy at doses of prednisone \> 10 mg/day or equivalent.
7. Prior allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
8. Prior ex vivo, in vivo, autologous or allogeneic CAR T therapy.
9. Prior treatment with investigational therapeutics that target CAIX or ENPP3.
10. Severe infection within 4 weeks prior to enrollment (e.g. patients requiring hospitalization, severe sepsis, or severe pneumonia with respiratory failure).
• Active ongoing infection requiring oral or IV antimicrobials prior to consenting.
Preventive antimicrobials are permitted
11. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
12. Pregnant women are excluded from this study because LNK001 is a CAR T agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LNK001, breastfeeding should be discontinued if the mother is treated with LNK001. These potential risks may also apply to other agents used in this study.
13. Patient is breastfeeding or plans to breastfeed during the study.
14. Patients with persistent non-hematological grade ≥2 adverse events per NCI CTCAE v6.0 from prior systemic therapies that would confound timely detection of adverse events due to LNK001 or otherwise hinder patient participation in the clinical trial.
15. History or current evidence of any condition (medical \[including adverse events from prior anticancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
Study of EV for Recurrent Endometrial Carcinoma
Enfortumab vedotin, a nectin-4-directed antibody-drug conjugate delivering the microtubule-disrupting agent MMAE, is being studied in patients with recurrent/progressive endometrial cancer that has progressed after platinum-based chemotherapy (and immunotherapy if eligible).
NCT07139977 · Phase 2 · William Bradley
Recruiting sites: Wisconsin
Read full eligibility criteria
Inclusion Criteria:
1. Female patient of age ≥18 years.
2. Recurrent and progressive endometrial cancer, all stages at primary diagnosis. The histology types will be pending the preclinical assessments, but can include:
1. Endometrioid endometrial carcinoma
2. Serous endometrial carcinoma
3. Prior standard of care of surgical intervention, including hysterectomy.
4. Evidence of disease progression on or following the most recent line of therapy prior to screening. Therapy must include platinum-based chemotherapy. If the patient is eligible for immunotherapy, this must have been provided. Patient may have received either radiation therapy or hormone therapy, neither of which will be considered a line of therapy. Chemotherapy during radiotherapy will not be considered a line of therapy.
5. Maximum of three prior lines of therapy. Neo-adjuvant and postsurgical therapy, if provided, will be counted as 1 line of therapy. Therapy given in a maintenance fashion after primary treatment will not be counted as a line of therapy.
6. IHC expression of nectin-4.
7. Toxicity from prior treatment recovered to G1 or G0.
8. ECOG status of 1 or 0.
9. At least 1 measurable target lesion according to RECIST v1.1, including the following criteria:
1. Non-nodal lesion that measures ≥ 1.0 cm in the longest diameter.
2. Lymph node (LN) lesion that measures as ≥ 1.5 cm in the short axis.
3. The lesion is suitable for repeat measurement using computed tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of subsequent growth after treatment.
10. Documented tumor status for MSI and MMR.
11. In the opinion of the investigator, the patient must have a life expectancy of at least 12 weeks and be well enough to receive experimental therapy.
12. Adequate organ function as determined by laboratory tests defined in the table below at screening.
Hematological: Absolutely neutrophil count (ANC)≥ 1500/μL, Platelets ≥ 100,000/μL, Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L, No erythropoietin dependency or packed red blood cell transfusion within last 2 weeks.
Renal: Creatinine, OR ≤ 1.5 x ULN, Creatinine clearance as calculated per institutional standard ≥ 30 mL/min for patients with creatinine \> 1.5 × institutional ULN Hepatic: Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ≤ 3 ULN for participants with Gilbert's syndrome. AST, ALT ≤ 3 × ULN (≤ 5 × ULN for participants with liver metastases
13. Ability to understand a written informed consent document, and the willingness to sign it.
14. Pregnancy: It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Nonsterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below. Female patients must meet one of the following:
1. Postmenopausal for at least one year before the screening visit, or
2. Surgically sterile, or
3. If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, AND
4. Must also adhere to the guidelines of any treatment specific pregnancy prevention program, if applicable, or
5. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.) Male patients/partners of patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
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1. Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
2. Must also adhere to the guidelines of any treatment specific pregnancy prevention program, if applicable, OR
3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)
Exclusion Criteria:
1. Diagnosis of endometrial sarcoma (leiomyosarcoma, endometrial stromal sarcoma, high-grade sarcoma).
2. Diagnosis of non-endometrioid and non-serous endometrial cancer. Mixed tumors involving histologic types other than serous and endometrioid will not be eligible.
3. Tumor sample does not express nectin-4 (local IHC testing).
4. Symptomatic CNS metastases or leptomeningeal metastases. Patients with symptomatic brain metastasis must be treated and must be stable for at least 4 weeks prior to study treatment.
5. Active second malignancy with anti-cancer treatments (except for treated in-situ carcinomas \[e.g., breast, cervix, bladder\], or basal or squamous cell carcinoma of the skin) within the past 24 months.
6. Sensory or motor neuropathy ≥ G2
7. Prior history of significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than New York Heart Association (NYHA)Class II, unstable angina, myocardial infarction, or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability.
8. Active infection requiring systemic IV antibiotics within 14 days, or oral antibiotics within 7 days, prior to administration of study drugs. Regular treatment of urinary tract infection (UTI) and/or topical treatment are allowed.
9. Uncontrolled diabetes defined as HgbA1c of ≥ 8%.
10. Hepatitis B, C, or HIV infection.
11. Have not recovered to CTCAE v5.0 Grade 0 or 1 (except chemotherapy related grade 2 peripheral neuropathy, or grade 2 endocrinopathy with adequate replacement therapy) from any toxicity and/or complications from major surgery or prior cancer therapeutics before starting therapy.
12. Ongoing treatment for EC, including radiation therapy, hormonal therapy, chemotherapy, immunotherapy, or any investigational therapy, unless they have been discontinued at least 4 weeks prior to screening and there is no plan to re-initiate during the study. radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities.
13. Active intestinal obstruction.
14. Known psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial.
15. Any conditions that required systemic immunosuppression therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) within 7 days prior to the first dose of study drug.
16. Pregnant or lactating patients.
17. In the opinion of the Investigator, have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or make study participation, not in the best interest of the patient. The Investigator should discuss with the Sponsor and/or study leaders.
Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System
This phase II trial compares subcutaneous amivantamab plus recombinant human hyaluronidase (a monoclonal antibody, with target not specified in the registry) against the EGFR-targeted monoclonal antibody cetuximab in immunocompromised patients with locally recurrent or metastatic cutaneous squamous cell carcinoma.
NCT07042295 · Phase 2 · National Cancer Institute (NCI)
Recruiting sites: Alabama, Arizona, California, Colorado, Connecticut, Florida, Georgia, Illinois, Indiana, Michigan, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, Texas, Utah, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Participants must have pathologically proven diagnosis of cutaneous squamous cell carcinoma based on pathology from original diagnosis or from a metastatic/recurrent lesion
* Participants must have measurable or non-measurable disease per RECIST 1.1 and must have their disease assessed by CT or MRI of chest/abdomen/pelvis (with contrast unless contraindicated) within 28 days prior to registration for measurable disease or within 42 days prior to registration for non-measurable disease. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Any lesions assessed using a non-diagnostic positron emission tomography (PET)/CT of chest/abdomen/pelvis will be considered non-measurable lesions. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration to be considered measurable
* NOTE: All diseases must be assessed and documented on the baseline tumor assessment form
* Participants with exclusively locally recurrent disease must have either a contraindication to surgical treatment of lesions (i.e., complete resection is not possible or not expected to be clinically beneficial or resection conferring significant cosmetic or functional concerns) or have refused surgical or radiation treatment
* Participants must be immunocompromised, defined as below. For cases where there is a lack of clarity, it is highly recommended study teams reach out to Drs. Swiecicki and Geiger for discussion:
* An diagnosis of either chronic lymphocytic leukemia (CLL), acute leukemia, myelodysplastic syndrome, polycythemia vera, or myelofibrosis regardless of whether actively receiving therapy OR
* A diagnosis of lymphoma or multiple myeloma either on antineoplastic therapy, or within 6 months after therapy completion OR
* Recipient of an organ transplant (excluding corneal transplants or lung transplants)
* If a transplant patient, documentation from the patient's transplant physician confirming that the patient's allograft is stable. Documentation must be dated within 180 days of registration OR
* Autoimmune disease under active treatment with an immunosuppressive medication (as defined below)
* Autoimmune diseases include but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, myasthenia gravis, Guillain-Barre syndrome, autoimmune hepatitis, scleroderma, primary biliary cirrhosis, pemphigus, and bullous pemphigoid
* Vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy are not eligible diagnoses
* Immunosuppressant medications include the following:
* Tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab, etanercept, golimumab, and infliximab)
* Interleukin inhibitors (anakinra, ustekinumab, secukinumab, sarilumab, siltuximab, sulfasalazine, tildrakizumab, tocilizumab, chloroquine, and hydroxychloroquine)
* Janus kinase (JAK) inhibitors (baricitinib, filgotinib, and tofacitinib)
* Calcineurin inhibitors (cyclosporine and tacrolimus)
* Metabolic inhibitors (azathioprine, leflunomide, mercaptopurine, methotrexate)
* mTOR (mammalian target of rapamycin) inhibitors (sirolimus \[rapamycin\], everolimus, and zotarolimus)
* Inosine monophosphate dehydrogenase inhibitors (mycophenolate)
* Phosphodiesterase inhibitors (apremilast)
* B cell inhibitors (rituximab)
* T cell inhibitors (abatacept)
* Glucocorticoids
* Active treatment is defined as current use of any one or more of the following:
* Oral glucocorticoid therapy (Prednisone equivalent \> 10 mg/day) for 30 days prior to registration
* Oral or subcutaneous immunosuppressive therapy for 90 days or more prior to registration
* Two or more doses of intravenous non corticosteroid immunosuppressant within 90 days prior to registration
* Participants with treated brain metastases must show no evidence of progression on follow-up brain imaging after central nervous system (CNS)-directed therapy
* Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate CNS specific treatment at the time of study registration or anticipated during the first cycle of therapy
* Participants must not have had prior treatment with cetuximab or another EGFR inhibitor within the last 365 days
* Participant must be ≥ 18 years old at the time of registration
* Participants must have Zubrod Performance Status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes ≥ 3 x 10\^3/uL (within 14 days prior to registration)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 14 days prior to registration)
* Platelets ≥ 100 x 10\^3/uL (within 14 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 14 days prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN with the exception of subjects with documented liver metastases: AST and/or ALT ≤ 5.0 x institutional ULN (within 14 days prior to registration)
* Participants must have a measured OR calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 14 days prior to registration
* Participants must not have an active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis
* Participants must not have a history of lung transplantation
* Participants must not have a history of pulmonary graft versus host disease (GVHD)
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* Participants with a history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* Participants with a history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants must not have an uncontrolled illness, including but not limited to:
* Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy \[participants will be required to complete antibiotics 1 week prior to starting study treatment\])
* Active bleeding diathesis
* Any ophthalmologic condition that is clinically unstable
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped) due to known toxicities of amivantamab. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants must agree not to donate ova or sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment. For female participants of childbearing potential, a negative pregnancy test is required within 72 hours prior to registration
* Participants must be offered the opportunity to participate in specimen banking
Zanzalintinib in Men With Aggressive Variant Prostate Cancer
Zanzalintinib (mechanism/target not stated in the registry) is being studied as a single-agent oral therapy in men with metastatic aggressive variant prostate cancer who have progressed after prior androgen receptor pathway inhibitor therapy.
NCT07218666 · Phase 2 · Deepak Kilari
Recruiting sites: Wisconsin
Read full eligibility criteria
Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
4. Histological or cytologically proven prostate cancer
5. Must have had evidence of metastatic disease (AJCC v.8 M1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
* Bone metastases detected by CT, radionuclide 99Tc- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria, OR
* Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥15 mm) detected on CT or MRI as defined by RECIST version 1.1. Subjects with regional lymph node metastases only (N1, below the aortic bifurcation) will not be eligible for the study; OR
* Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm.
6. Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone \< 50 ng/ dL (\< 1.73 nmol/L) at screening.
7. Must have progressed during or after at least one second-generation androgen receptor pathway inhibitor (abiraterone acetate, enzalutamide, apalutamide, darolutamide) given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 castrate- resistant prostate cancer (CRPC), or metastatic CRPC.
Note: Subjects may have previously received taxane-based chemotherapy for metastatic castration-sensitive prostate cancer (mCSPC), and sipuleucel-T, olaparib, Pluvicto (Lutetium (177Lu) vipivotide tetraxetan), and/or radium-223 for castrate -resistant prostate cancer. The number of patients who have received both taxanes and/or platinum in a CRPC setting will be limited to 5/15 in the first stage and thereby sponsor investigator approval is required prior to enrollment of patients who meet above criteria.
8. Presence of at least one of the following:
* Presence of visceral metastases or high-volume disease (\> 4 sites of metastases) on conventional imaging (CT/MRI/bone scan) with a PSA ≤ 5.
* Predominantly lytic bone metastasis.
* Bulky (≥5 cm) lymphadenopathy OR bulky (≥5 cm) high-grade (Gleason ≥8) tumor mass in the prostate/pelvis.
* Serum chromogranin A level ≥ 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2× ULN.
* Prostate adenocarcinoma with IHC staining for neuroendocrine markers (positive staining of chromogranin A or synaptophysin).
* Alterations in at least two of the three tumor suppressor genes: TP53, RB1 and PTEN on genomic testing.
* Progression to CRPC within 6 months or less of initiation of hormonal therapy.
* Poorly differentiated or transdifferentiated carcinoma.
* PSMA negative/FDG avid disease on PET scan.
9. Recovery of adverse events (AEs), including immune-related adverse events (irAEs), to baseline or ≤ Grade 1 severity (CTCAE v5) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted.
10. Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
* Platelets (Plt) ≥ 100,000/mm3 without transfusion within 2 weeks of sample collection
* Absolute Neutrophil Count (ANC) ≥ 1500/mm3 without granulocyte colony-stimulating factor support within 2 weeks of sample collection
* Hemoglobin (Hgb) ≥ 9 g/dL without transfusion within 2 weeks of sample collection.
* Calculated creatinine clearance1 ≥ 40 mL/min
* Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine
* Total bilirubin ≤1.5 × upper limit of normal (ULN); ≤ 3 × ULN for subjects with Gilbert's disease
* Aspartate aminotransferase (AST) ≤ 3 × ULN
* Alanine aminotransferase (ALT) ≤ 3 × ULN
* Alkaline phosphatase (ALP) ≤ 3 × ULN; ≤ 5 × ULN for subjects with documented bone metastasis; ≤ 10 x ULN for subjects with CRPC and bone metastasis if predominantly bone-specific ALP
* International Normalized Ratio (INR) ≤ 1.5 × ULN
* Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 × ULN
11. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for 96 days after the last dose of study drug.
12. Projected life expectancy of at least 6 months as determined by treating investigator.
13. Ability of the subject to understand and comply with study procedures for the entire length of the study as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
1. Pure small cell carcinoma of the prostate.
2. Prior treatment with zanzalintinib.
3. Imminent or established spinal cord compression based on clinical and/or imaging findings.
4. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study drug.
5. Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of start of investigational agent and during the study. Concomitant use of megestrol acetate or leuprolide is permitted. The anti-androgen abiraterone is permitted up to 1 week prior to the first dose of study drug. Other types of hormonal therapies with similar use require prior approval of the Sponsor Investigator.
6. Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study drug. Systemic treatment with radionuclides within 6 weeks before first dose of study drug are not permitted. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
7. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study drug. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
8. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). Note: Subjects must discontinue prohibited oral anticoagulants within 3 days or 5 half-lives prior to first dose of study drug, whichever is longer.
The following anticoagulants are allowed:
1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study drug without clinically significant hemorrhagic complications from the anticoagulation regimen.
9. Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study drug.
10. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
a. Unstable deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study drug.
iv. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study drug.
Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study drug without clinically significant hemorrhagic complications from the anticoagulation regimen.
Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Sponsor Investigator.
b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI-tract from external viscera. ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic.
iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study drug.
v. Known gastric or esophageal varices. vi. Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks before first dose of study drug.
11. Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study drug.
12. Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed)
13. Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava) may be eligible following Sponsor Investigator approval.
14. Other clinically significant disorders that would preclude safe study participation.
a Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
b Known infection with acute or chronic hepatitis B or C. Note: Hepatitis B and C testing will be performed at screening.
c Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for subjects meeting all of the following criteria: i. on stable anti-retroviral therapy, and ii. CD4+ T cell count ≥ 200/µL, and iii. an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation.
Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose.
Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider.
c Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
d Malabsorption syndrome e Pharmacologically uncompensated, symptomatic hypothyroidism f Moderate to severe hepatic impairment (Child-Pugh B or C) g Requirement for hemodialysis or peritoneal dialysis. h History of solid organ or allogeneic stem cell transplant.
15. Major surgery (as defined in Section 5.2.5; eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 5 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study drug. Note: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
16. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms per electrocardiogram (ECG) performed within 14 days before first dose of study treatment. Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
17. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
18. Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
19. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
20. Prior malignancy which required active therapy within 2 years before first dose of study drug.
Notes:
* Inclusion of patients with prior malignancies is allowed if the risk of the prior malignancy interfering with either safety or efficacy end points is very low, as assessed by the treating investigator.
* Patients with a previously treated malignancy are eligible to participate if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease.
* Patients who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are allowed to participate.
21. Other conditions which, in the opinion of the treating Investigator, would compromise the safety of the patient or the patient's ability to complete the study.
A Clinical Trial of Ifinatamab Deruxtecan in People With Advanced Esophageal Cancer (MK-3475-06F)
Ifinatamab deruxtecan (I-DXd), an antibody-drug conjugate, is being studied in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma who have progressed after 1-2 prior lines of systemic therapy.
NCT07405151 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
* Has a histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
* Has disease progression after 1 or 2 prior lines of systemic therapy for unresectable locally advanced or metastatic ESCC
* Has measurable disease
* If infected with human immunodeficiency virus (HIV), has well-controlled HIV on antiretroviral therapy
* Has adequate organ function
Exclusion Criteria:
* Has histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma subtype
* Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
* Has clinically significant corneal disease
* Has any of the following within 6 months before screening: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event
* If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has uncontrolled or significant cardiovascular disease
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system metastases and/or carcinomatous meningitis
* Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids or has current diagnosis of ILD or has clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
* Has active infection requiring systemic therapy other than those permitted.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen
A Phase IIIb Study to Evaluate Camizestrant Plus Ribociclib in ER-positive, HER2-negative Advanced Breast Cancer
Phase IIIb trial of camizestrant (an oral SERD that degrades the estrogen receptor) combined with ribociclib (a CDK4/6 inhibitor) as first-line therapy for previously untreated locoregionally recurrent or metastatic ER-positive, HER2-negative breast cancer.
NCT07647328 · Phase 3 · AstraZeneca
Recruiting sites: California, Georgia, Illinois, Kentucky, Nevada, South Dakota, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Capable of giving signed informed consent.
2. Female or male, must be ≥ 18 years or as per locally allowed age limit for screening.
Type of Participant and Disease Characteristics
3. Histologically or cytologically documented diagnosis of ER+, HER2- BC based on local laboratory results and who are not amenable to resection or radiation therapy with curative intent.
4. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease.
5. De novo Stage 4 disease, or recurrence from early CD stage breast cancer after having received standard adjuvant endocrine therapy. Note that at least 12 months must have elapsed since the patient's last dose of adjuvant AI therapy without disease progression on treatment. Note that a 2-week washout period is required after the last dose of tamoxifen prior to randomisation.
6. ECOG performance status of 0 or 1.
7. Adequate organ and marrow function. Sex and Contraceptive/Barrier Requirements
8. For those female or male patients who are not abstinent (in line with their preferred and usual lifestyle choice), and intend to be heterosexually active with a partner:
Female patients must be using highly effective contraceptive measures from the time of screening until 4 weeks after discontinuation of study treatment, and must have a negative serum pregnancy test before first dose of any study treatment if they are of childbearing potential; or must have evidence of nonchild-bearing potential by fulfilling one of the following criteria at screening:
(a) Post-menopausal, defined as women with cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause: (i) Age ≥ 60 years (ii) Age \< 60 years with serum estradiol and FSH level within the laboratory's reference range for post-menopausal females (iii) Previous bilateral surgical oophorectomy (iv) Medically confirmed ovarian failure OR (b) Pre/peri-menopausal, ie, not meeting the criteria for being post-menopausal.
(i) Pre-/peri-menopausal women can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin \[also known as leuprolide\]). Patients must have concomitant treatment with LHRH agonists (goserelin or leuprorelin \[leuprolide\]) before or on the same day as the first dose of study treatment - and must be willing to continue on it for the duration of the study.
Non sterilised male partners of a patient who is a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period.
Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening throughout the total duration of the programme and the drug washout period to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period.
Male patients can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin \[also known as leuprolide\]) unless the patients have clear orchiectomy medical history. Willingness to use 2 non-hormonal based methods of contraception throughout the study.
Exclusion Criteria:
1. Participants who are not clinically indicated for endocrine therapy in combination with the CDK4/6 inhibitor ribociclib.
2. No evidence of advanced inoperable disease, or bone only disease with sclerotic/osteoblastic bone lesions only per standard of care imaging.
3. Have advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term, and/or pulmonary lymphangitis.
4. Persistent treatment-induced non-haematological toxicities (CTCAE Grade \> 2).
5. Known active infection including tuberculosis HBV and HCV.
6. Known to have tested positive for HIV. Participants with HIV may be enrolled if they fulfil the criteria recommended by FDA and ASCO guidelines.
7. Any clinically important abnormalities in heart conduction patterns; participants with pacemakers or medically controlled atrial fibrillation are not excluded.
8. Ongoing symptomatic hypotension.
9. Pregnant or lactating women or patients not willing to use highly effective contraception as defined in the protocol.
Cs-131LDR Brachytherapy for Organ-Preserving Irradiation for Recurrent Cervical and Endometrial Cancer
This trial uses Cesium-131 low-dose-rate interstitial brachytherapy (permanent radioactive seed implant) as an organ-preserving salvage radiation technique for vaginal recurrence of cervical or endometrial cancer following prior pelvic radiation therapy.
NCT07631572 · Phase N/A · Denise Fabian
Recruiting sites: Kentucky
Read full eligibility criteria
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed vaginal recurrence of endometrial (endometrioid adenocarcinoma, uterine serous, carcinosarcoma, clear cell) or cervical (squamous, adenosquamous, or adenocarcinoma) cancer and prior history of pelvic radiation.
* Patients must have vaginal recurrence that is amenable to cesium implant for salvage
* Patients must have a vaginal lesion that is measurable according to RECIST 1.1 criteria; that is, at least 1 cm upon measurement by CT, or MRI if the patient cannot have a CT with contrast or lesion is not visualized on CT scan, or measurement by calipers if the lesion is not seen on CT or MRI.
* Patients must have previous external beam radiation treatment to the pelvis for the uterine cervix or endometrial malignancy that has recurred to be eligible for this study, so long as the prior exposure does not exceed tolerance at the discretion of the treating physician.
* Gynecologic Oncology Group performance status of 0, 1, or 2 (see Appendix A).
* There are no minimum organ/marrow function requirements because patients will not be receiving systemic therapy.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Patients who have another concurrent, active invasive malignancy or have had a prior invasive malignancy diagnosed within the last three years, with the following two exceptions: \[a\] non-melanoma skin cancer and/or \[b\] prior in situ carcinoma of the cervix and/or \[c\] in situ bladder cancer.
* Patients who have metastatic or regional lymph node metastases who have radiographic evidence of disease at time of study enrollment. Patients who have had metastasis or lymph nodes previously treated without radiographic disease at time of study enrollment may be considered at discretion of the treating radiation oncologist.
* Receipt of epoetin alpha (Procrit, Epogen) within 1 month of study screening.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cesium-131 implant or other agents used in this study.
* Pregnant women are excluded from this study because radiation is a known teratogen. Patient must agree to use two forms of birth control if they are of child-bearing potential. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout duration of active treatment and for two months after completion of radiation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
First-Line Ipilimumab Plus Nivolumab and Nogapendekin Alfa Inbakicept (N-803) in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
This trial studies the combination of ipilimumab (anti-CTLA-4), nivolumab (anti-PD-1), and nogapendekin alfa inbakicept (IL-15 agonist) as first-line treatment for stage IV or recurrent metastatic non-small cell lung cancer.
NCT07355205 · Phase 1/2 · Washington University School of Medicine
Recruiting sites: Missouri
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed, previously untreated or recurrent metastatic NSCLC.
* Availability of archival biopsy tissue or willingness to undergo a biopsy prior to C1D1 for biomarker analysis, including PD-L1 by IHC using a CLIA-certified test. Results of the PD-L1 testing are not required for enrollment.
* Measurable disease per RECIST 1.1.
* At least 18 years of age.
* ECOG performance status ≤ 1
* Adequate organ and marrow function, as defined below:
* Absolute neutrophil count ≥ 1.5 K/cumm
* Platelets ≥ 100 K/cumm
* Hemoglobin ≥ 9.0 g/dL
* AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5 x IULN with hepatic metastasis
* Total bilirubin ≤ 2 x IULN (except participants with Gilbert's syndrome who must have total bilirubin \< 3.0 mg/dL)
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* INR ≤ 1.5 unless using therapeutic anticoagulation
* PTT/aPTT \< 1.5 x IULN unless using therapeutic anticoagulation
* Patients with brain metastases are eligible if they have previously treated with surgery or radiation therapy, are neurologically stable after a washout period of at least 2 weeks, and are not receiving corticosteroids at dose higher than 10 mg of prednisone or equivalent on C1D1.
* The effects of the treatment regimen on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use highly effective methods of contraception, according to the protocol, from the time of consent through 6 months after the last dose of study treatment.
* Ability to understand and willingness to sign an IRB-approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* Mixed histology including small cell lung cancer.
* Tumor harboring any of the following:
* classic EGFR mutations
* HER2 mutation
* ALK fusion
* ROS1 fusion
* RET fusion
* NTRK fusion
* MET Exon14 skipping mutation
* BRAF V600E mutation
* Use of any live vaccines within 28 days of C1D1.
* Prior chemotherapy in the adjuvant setting or during concurrent radiation therapy for locally advanced disease within 12 months prior to enrollment. If the interval from the last treatment is 12 months or longer, the patient is eligible.
* Radiation therapy within 14 days prior to C1D1.
* History of major surgery within 14 days prior to C1D1.
* Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous, including but not limited to:
* History of interstitial lung disease or noninfectious pneumonitis,
* Active viral, bacterial or fungal infections requiring parenteral treatment within 14 days of C1D1,
* Clinically significant cardiovascular disease,
* A condition that may obscure the interpretation of toxicity determination or AEs,
* History of prior solid-organ transplantation.
* Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (\> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids are not excluded).
* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
* Evidence of chronic hepatitis B (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
* Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
* Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study.
* Participants on chronic systemic corticosteroids will be excluded from the study.
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
* Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of C1D1.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study, or known hypersensitivity to recombinant proteins, or any excipient contained in the trial formulations.
* Pregnant and/or breastfeeding. People of childbearing potential must have a negative pregnancy test within 7 days of study entry.
ILKN421H Plus Pembrolizumab in Advanced Non-Small Cell Lung Cancer
ILKN421H (mechanism not stated in the registry) plus pembrolizumab is studied in locally advanced or metastatic NSCLC, in both post-PD-1/L1-inhibitor and first-line PD-L1-positive treatment-naive settings.
NCT07452224 · Phase 2 · iLeukon Therapeutics, Inc.
Recruiting sites: California, Texas
Read full eligibility criteria
Inclusion Criteria:
To be enrolled in this study, participants must meet all the following inclusion criteria:
1. Provide written informed consent after full understanding of the study.
2. Adults at least 18 years of age.
3. ECOG performance status of 0 or 1.
4. Life expectancy ≥12 weeks.
5. At least one measurable lesion per iRECIST/RECIST 1.1 criteria, defined as:
Lymph node lesion with short axis ≥1.5 cm or non-lymph node lesion with longest diameter ≥1 cm on CT/MRI; If the only lesion has undergone prior local treatment (radiotherapy, ablation, vascular intervention, etc.), there must be clear imaging evidence of disease progression in this lesion after local treatment.
6. Participants must have locally advanced or metastatic NSCLC, confirmed by available pathology records or current biopsy, that is advanced (non-resectable), or recurrent, for which no alternative, curative standard therapy exists. For Cohort 1 and Cohort 2, pathologically or cytologically confirmed advanced malignant locally advanced or metastatic NSCLC participants who have failed standard PD-1/L1 inhibitor alone or in combination with standard chemotherapy treatment regardless of PD-L1 expression. For Cohort 3 and Cohort 4, participants with pathologically or cytologically confirmed advanced, non-resectable locally advanced or metastatic NSCLC, who have previously untreated with any anticancer drugs expressing PD-L1 (TPS≥ 1%) as determined by an FDA-approved test.
7. Adequate organ and marrow function within 7 days before first dose, as defined below:
1. Absolute neutrophil count (ANC) ≥1.5×10⁹/L
2. Platelets (PLT) ≥100×10⁹/L
3. Hemoglobin (HGB) ≥90 g/L
4. Alanine aminotransferase (ALT) ≤2.5×ULN (≤5×ULN if known liver involvement)
5. Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if known liver involvement)
6. Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN if diagnosed with Gilbert's syndrome)
7. Serum creatinine ≤1.5×ULN or estimated glomerular filtration rate (eGFR, calculated by Cockcroft-Gault formula or 24-hour urine measurement) ≥40 mL/min
8. International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN No component blood transfusion within 14 days prior to the above testing, and no supportive treatments (e.g., G-CSF, TPO, TPO receptor agonists, IL-11, EPO) within 7 days of above testing.
8. For Cohort 1 and Cohort 2, prior anti-tumor treatment-related toxicities resolved to ≤ Grade 1 (excluding Grade 2 neurotoxicity, Grade 2 hypothyroidism, any grade alopecia and pigmentation, and Grade 2 AEs that cannot resolve to ≤Grade 1 but remain stable long-term as judged by the investigator based on clinical practice; laboratory parameters refer to Inclusion Criteria 7).
9. Willing and able to comply with study schedules and all protocol requirements.
10. Women must meet one of the following criteria: postmenopausal for at least 24 consecutive months; surgically incapable of bearing children (i.e., have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception (either medication \[oral, implant, or injection\] or a barrier method). In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the participant to use a reliable form of contraceptive during the study Treatment Period and for at least 70 days following the last dose of study drug (Appendix IV). Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product; and Men must agree to the use of contraception during the study Treatment Period and for at least 180 days after the last dose of study drug.
Exclusion Criteria:
To be included in this study, participants must not meet any of the following exclusion criteria:
1. Known allergy to any component of the investigational drug formulation or IL-2.
2. Participation in any therapeutic clinical study and receiving treatment within 28 days prior to the first dose, excluding observational studies or survival follow-up stages of interventional studies.
3. Use of immunomodulatory drugs within 14 days or 5 half-life (whichever is longer) before the first dose, including but not limited to thymosin, IL-2, IL-15, interferon, etc.
4. Received chimeric antigen receptor T-cell (CAR-T) immunotherapy within 3 months prior to the first dose; chemotherapy (≥6 weeks for nitrosoureas and mitomycin C, ≥14 days for oral fluoropyrimidines), endocrine therapy, targeted therapy (with a washout period of 14 days or 5 half-lives, whichever is longer), immunotherapy (see exclusion criterion 3 for immunomodulatory drugs), tumor embolization, etc., within 28 days prior to the first dose; radiotherapy within 14 days before the first dose, except for palliative radiotherapy, which must be completed at least 7 days prior to the first dose; Exceptions may be allowed if, based on investigator assessment, the subject is still eligible for enrollment.
5. Major surgery within 28 days prior to the first dose or minor surgery within 7 days prior to the first dose, or having unhealed wounds, ulcers, or fractures, or requiring elective surgery during the study (except for diagnostic biopsy or insertion of vascular access devices).
6. Vaccination with live attenuated vaccines within 28 days prior to the first dose or planned during the study.
7. Use of systemic immunosuppressive agents within 28 days prior to the first dose, except for:
1. Intranasal or localized corticosteroids (e.g., intra-articular injection);
2. Systemic corticosteroids ≤ 10 mg/day prednisone or equivalent dose;
3. Corticosteroids for preventing allergic reactions (e.g., pre-chemotherapy);
4. Corticosteroids for preventing infusion reactions;
8. Known or confirmed central nervous system (CNS) metastases or carcinomatous meningitis during screening.
9. Uncontrolled third-space fluid accumulation requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (participants without the need for drainage or who have not had significant accumulation after ceasing drainage for 3 days can be included), or blood-tinged third-space fluid confirmed by diagnostic aspiration.
10. History of any other malignant tumors within 5 years prior to the first dose, except for cured early-stage malignancies (e.g., carcinoma in situ or stage I tumors), such as adequately treated basal or squamous cell carcinoma of the skin, surgically resected carcinoma in situ of the cervix or breast, early-stage papillary thyroid carcinoma, or prostate cancer with a Gleason score ≤ 6.
11. Active autoimmune diseases or inflammatory diseases \[including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), diverticulitis (excluding diverticular disease), celiac disease, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis, etc.\], or a history of such diseases within the past 2 years (participants with conditions such as vitiligo, psoriasis, alopecia, or controlled hypothyroidism or type 1 diabetes requiring only thyroid hormone replacement or insulin therapy are allowed).
12. Active or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA), HCV (HCV-Ab positive with positive HCV RNA), or HIV positive.
13. Active bacterial, viral, or fungal infection within 72 hours prior to the first dose (defined by persistent signs/symptoms of infection despite appropriate treatment) or requiring intravenous (i.v.) antibiotics therapy.
14. Severe or uncontrolled cardiovascular or cerebrovascular diseases requiring treatment, including but not limited to:
1. New York Heart Association (NYHA) Class \> 2 heart failure (Appendix II);
2. Unstable angina uncontrolled by medication;
3. Myocardial infarction within 6 months prior to the first dose;
4. History of myocarditis;
5. Pericardial tamponade;
6. Uncontrolled arrhythmia (e.g., ventricular tachycardia during antiarrhythmic treatment-participants with grade I atrioventricular block or asymptomatic left bundle branch block/right bundle branch block are not excluded);
7. QTcF \> 470 msec on 12-lead ECG;
8. Left ventricular ejection fraction (LVEF) \< 50%;
9. Uncontrolled hypertension (defined as blood pressure not at targeted level despite ≥1 month of treatment with at least two reasonable and tolerated antihypertensive medications following lifestyle modifications, or blood pressure that can only be effectively controlled with four or more antihypertensive medications) or hypotension;
10. Stroke, cerebrovascular accident, or transient ischemic attack within 6 months prior to the first dose.
15. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of the predicted normal value. Suspected COPD participants must undergo FEV1 testing; those with FEV1 \< 50% predicted normal value must be excluded.
16. Known moderate or severe persistent asthma, a history of asthma within the past 2 years, or currently uncontrolled asthma (note: participants with intermittent asthma or mild persistent asthma under control are eligible).
17. History of interstitial lung disease (including drug-induced), pneumoconiosis, pulmonary fibrosis, or severe pulmonary dysfunction; active tuberculosis, currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within the past year.
18. Significant clinical bleeding symptoms within 3 months before the first dose, including hemoptysis of any significant amount (≥ 2.5 mL per episode) within 28 days prior to the first dose.
19. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.
20. History of deep vein thrombosis, pulmonary embolism, or other severe thromboembolic events within 3 months prior to the first dose (excluding thrombosis caused by vascular access devices or superficial venous thrombosis).
21. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or worse cirrhosis.
22. Known history of primary immunodeficiency.
23. Known history of organ transplantation or allogeneic hematopoietic stem cell transplantation (corneal transplantation excluded).
24. Pregnant or breastfeeding women.
25. Any active severe psychiatric disorder, medical disease, or other condition that may interfere with treatment, compliance, or the ability to provide informed consent, as determined by the investigator.
26. A history of allergy to pembrolizumab.
27. A history of permanent discontinuation of pembrolizumab or similar drugs due to drug-related adverse events (AEs).
28. Potential participants may be excluded if, in the judgment of the Principal Investigator (PI), their participation would pose an unacceptable risk to their safety or significantly compromise the integrity or interpretability of the study's efficacy endpoints.
Trial of Therapies With IT cDC1s Combined w/ IT Trastuzamab for Her+ or IT Nivolumab for Her- BC LMD
This phase 2 trial evaluates an intrathecal autologous peptide-pulsed cDC1 dendritic cell vaccine combined with intrathecal trastuzumab (HER2-positive) or intrathecal nivolumab (HER2-negative) in patients with breast cancer complicated by leptomeningeal disease.
NCT07694986 · Phase 2 · H. Lee Moffitt Cancer Center and Research Institute
Recruiting sites: Florida
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of BC by ASCO/CAP guidelines (Wolff et al, 2018), or radiographically definite LMD from BC.
* Trial participants must have a diagnosis of LMD. They must have the presence of malignant cells in the CSF (CSF+; note now cytology is considered diagnostic of LMD if the cytology is read as positive or suspicious; \[Chamberlain et al., 2017\] OR characteristic radiographic abnormalities of LMD). Signs and symptoms of LMD in and of themselves are not sufficient for inclusion.
* Patients must have an ECOG performance scale of ≤2.
* Proton cranial spinal RT OR cranial spinal RT using IMRT are the preferred modalities of RT to treat LMD if possible, before study. At least WBRT is required for participation.
* Coincident brain or spinal cord metastases are allowed if these are stable and do not require local therapy at the time of enrollment. Individuals with previously treated stable brain metastases are eligible to participate.
* Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted ≥2 weeks before the initial dendritic cell (DC) vaccine dose. A follow-up brain MRI should be obtained before the DC vaccine to determine the stability of the lesions. An interval of at least 2 weeks after the end of brain radiation or surgical resection of brain lesions or cytotoxic, targeted, immune, or investigational agent is required.
* Must be ≥18 years of age on the day of signing the consent.
* Life expectancy of ≥8 weeks.
* Demonstrate adequate organ function as defined in Table 5. All screening labs should be performed within 14 days of treatment initiation.
* Ability to understand and the willingness to sign a written informed consent document.
* Corticosteroids at doses equivalent to ≤4 mg of dexamethasone daily or equivalent for symptom control are acceptable. This should be minimized when possible.
* If the disease has progressed on current treatment before consent, patients may continue current systemic cancer therapies by PI discretion see Section 7.7.5 (Systemic Therapies Allowed) and Section 5.2, 1 and 2 (Exclusion Criteria).
* Patients with systemic disease are eligible and will be managed as detailed in Section 7.7.5.
* Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential. Must be repeated once a month during treatment.
* Contraception: Highly effective contraception for both male and female subjects throughout the study, and for the following specified durations after the last treatment administration as follows: highly effective contraception must be used by males for at least 90 days after the last treatment administration, if the risk of conception exists, to cover the spermatogenesis Cycle, and at least 5 months after the last dose of nivolumab or 7 months after the last dose of trastuzumab for females.
* The patient has an Ommaya reservoir or equivalent device that allows routine access to CSF and administration of DC1s.
* Patient must be able to tolerate MRIs of brain with contrast for routine disease assessments.
Exclusion Criteria:
* Receiving other treatments specifically administered to treat LMD within the last 2 weeks or 5 half-lives of the agent, whichever is less. However, all other treatments to control systemic disease or bulk CNS disease will be eligible, provided the therapy is not a Phase I agent, an agent that significantly and unequivocally penetrates the CSF (eg, high-dose methotrexate, thiotepa, high-dose ara-C) by PI discretion. H \& P section: Patients may continue on IV trastuzumab, fam-trastuzumab deruxtecan-nxki, pertuzumab, tucatinib, or other HER2-directed, hormonal, or other therapeutic agents if controlling systemic disease and leptomeningeal metastases developed while on these therapies. In addition, at time of systemic progression, patients may start additional agents at the discretion of the treating physician according to criteria in Section 6.7.1. and not start on new systemic therapies until LMD disease assessment.
* Use of any immunotherapy within the last 4 weeks.
* Unable or unwilling to have a contrast-enhanced brain MRI.
* Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
* Has an active infection requiring systemic therapy which in the investigator's opinion will increase the risk to the patient.
* Had major surgical procedure, or significant traumatic injury within 2 weeks. Ommaya placement is allowed.
* Patients with shunts are excluded from the study (including but not limited to ventriculoperitoneal and ventriculoatrial shunts).
* History of an intracranial thrombosis or thrombi extending up to the skull base. The choice of modality is at the investigator or provider's discretion.
* Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment.
* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1, 2 antibodies). Testing is not mandatory.
* Has known active or chronic hepatitis B (HBV) or hepatitis C virus (HCV). Testing is not mandatory.
* ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.
* Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Has received a live vaccine within 30 days before the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed. Current COVID vaccines are not live vaccines.
A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer
VS-7375, an oral KRAS G12D inhibitor, is being studied alone or combined with cetuximab, panitumumab, or cetuximab plus mFOLFOX6 in patients with KRAS G12D-mutated metastatic colorectal cancer in first-line or later lines.
NCT07659795 · Phase 2 · Verastem, Inc.
Recruiting sites: Arizona, California, Florida, Indiana, Michigan, Missouri, New Jersey, New York, North Carolina, Ohio, Tennessee, Texas, Utah, Virginia, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Histopathology confirmed metastatic CRC
* Measurable disease per RECIST 1.1
* Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
* ECOG PS=0 or 1
2L+ patients:
* Must have received at least 1 standard chemotherapy for metastatic colorectal adenocarcinoma
* Have documented disease progression during or following their most recent prior line of therapy
* Have either stable disease, partial response (PR), or complete response (CR) by RECIST v1.1 as the best overall response (BOR) during at least 1 prior systemic therapy.
1L patients:
* Treatment-naïve or received no more than 1 cycle of standard systemic therapy for metastatic disease.
Exclusion Criteria:
* Have any other documented co-existing common RAS mutation(s)
* Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
* Major surgery within 4 weeks of first treatment dose
* Radiation therapy (RT) within 1 week of first treatment dose
* Receipt of prior direct RAS inhibitor
* Receipt of more than 1 investigational therapy
* Untreated or symptomatic CNS metastasis
* Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
* Receipt of PPI or H2 blocker within 5 days
* Inability to swallow oral medication
* Other protocol-defined inclusion/exclusion criteria may apply
A Study of Theranostic Pair PD-32766D/T in Participants With Carbonic Anhydrase IX Positive Clear Cell Renal Cell Carcinoma
PD-32766T, an Actinium-225-labeled peptide targeting carbonic anhydrase IX, is being studied as a radioligand therapy in relapsed/refractory clear cell renal cell carcinoma after standard therapy.
NCT07688187 · Phase 1 · PeptiDream Inc.
Recruiting sites: Nebraska
Read full eligibility criteria
Inclusion Criteria:
1. Male or female participants aged ≥18 years.
2. Participants with confirmed diagnosis of ccRCC will be included based on the following characteristics:
* Histological confirmed locally advanced, unresectable, or metastatic ccRCC, after all available standard therapy.
* Presence of evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) guideline (defined by RECIST v1.1).
3. Presence of positive tumor uptake
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
5. The participant's with adequate organ function
6. Life expectancy of at least 12 weeks as assessed by the Investigator.
Exclusion Criteria:
1. Concurrent serious (as determined by the Investigator), uncontrolled medical conditions, or life-threatening or other significant comorbid conditions.
2. Any chemotherapy, radiotherapy, immunotherapy, major surgery, biologic, investigational or hormonal therapy for treatment of solid tumors within 28 days.
3. Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy.
4. Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months.
5. Any previous CA9 targeting treatment.
6. Known hypersensitivity to the active substance or to any of the excipients of the PD-32766D and or T.
7. Clinically unstable CNS tumor at the time of screening.
8. History of bowel perforation or bowel infarction, history of active stomach or duodenum ulcer or fistula in the last 2 years, history of gastroesophageal reflux disease or enterocolitis Grade ≥3 according to NCI-CTCAE and/or known active gastrointestinal infection, any unresolved prior radiation-induced gastrointestinal injury.
9. Acute infection requiring IV antibiotics, antivirals, or antifungals within 14 days prior to the initiation of treatment (oral treatment are allowed).
10. Pregnant or breastfeeding women.
11. Known active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
12. Have been diagnosed with another primary malignancy.
13. Have significant, uncontrolled, or active cardiovascular disease
14. Bladder outflow obstruction or unmanageable urinary incontinence.
15. Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
16. Any major surgery within 12 weeks before enrolment.
17. History of psychiatric illness or social situations likely to interfere with ability to comply with protocol required assessment or give informed consent.
Adaptive Daily MR-Guided Adjuvant Pelvic Therapy-Endometrial Cancer
This trial delivers MR-guided adaptive pelvic intensity-modulated radiation therapy (IMRT), a hypofractionated 15-fraction radiotherapy regimen via MR-linac, as adjuvant treatment for patients with high-intermediate risk endometrial cancer.
NCT07643012 · Phase N/A · Rutgers, The State University of New Jersey
Recruiting sites: New Jersey
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed endometrial carcinoma (endometrioid, serous, clear cell, carcinosarcoma, or dedifferentiated histology).
2. Indication for adjuvant pelvic radiotherapy (± vaginal brachytherapy) for HIR defined by the ASTRO guidelines and GOG-99(7, 9) :
3. Age
4. High-grade histology (grade 2-3)
5. Depth of myometrial invasion
6. LVSI
7. Positive pelvic nodes
8. Cervical stromal invasion
9. Presence of poor prognostic molecular markers
10. Age ≥18 years.
11. Ability to provide informed consent.
12. Eligible to receive adjuvant systemic therapy, if indicated, with a minimum 3-week interval between chemotherapy and radiotherapy.
13. Willing and able to complete EORTC QLQ-C30 and EN-24 questionnaires in a validated language version.
Exclusion Criteria:
1. Prior pelvic radiotherapy.
2. Contraindication to pelvic radiotherapy (e.g., active connective tissue disorder or inflammatory bowel disease).
3. Presence of a hip prosthesis that would compromise treatment planning or delivery.
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Evaluation of Alternative Site Goserelin Acetate Injection for Ovarian Function Suppression (OFS) in Local and Locally Advanced Premenopausal Hormone Receptor Positive Breast Cancer Patients
Goserelin acetate (an LHRH agonist used for ovarian function suppression as part of endocrine therapy) is compared via alternative injection site (gluteal vs abdominal) in premenopausal patients with stage I-III hormone receptor-positive breast cancer already receiving OFS plus aromatase inhibitor or tamoxifen.
NCT07460752 · Phase 2 · Mayo Clinic
Recruiting sites: Minnesota
Read full eligibility criteria
Inclusion Criteria:
* REGISTRATION (STEP 1): Age ≥ 18 years and ˂ 50 years
* REGISTRATION (STEP 1): Have histologically or cytologically confirmed, localized or locally advanced hormone positive breast cancer stage I-III (defined as ER Immunohistochemistry (IHC) \> 1%\] having completed curative intent therapy and clinically in remission
* REGISTRATION (STEP 1): Currently receiving ovarian function suppression (OFS) with use of goserelin on a monthly basis in the abdomen and either aromatase inhibitor or tamoxifen for at least 6 months prior to study enrollment for treatment of hormone receptor positive breast cancer with plan to continue medical OFS for at least the next 12 months
* REGISTRATION (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* REGISTRATION (STEP 1): Provide written informed consent
* REGISTRATION (STEP 1): Ability to complete questionnaire(s) by themselves or with assistance
* REGISTRATION (STEP 1): Willingness to provide mandatory blood specimens for correlative research
* REGISTRATION (STEP 1): Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* REGISTRATION (STEP 1): Negative serum pregnancy test =\< 14 days prior to registration, and a negative urine pregnancy test =\< 7 days prior to randomization
* REGISTRATION (STEP 1): Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry and for the duration of study participation and for at least 3 months after the last dose of study drug.
* Note: The following are considered effective contraceptives: oral contraceptive pill; condom plus spermicide; diaphragm plus spermicide; patient or partner surgically sterile; patient or partner more than 12 months postmenopausal; or injectable or implantable agent/device. Male patients should refrain from sperm donation and female patients should refrain from breastfeeding throughout this period
* RANDOMIZATION (STEP 2): Completion of the lead-in treatment of 6 cycles of ovarian function suppression (OFS) with use of goserelin, with estradiol E2 value of ˂ 20 pg/mL and no back to back E2 levels \> 10 pg/mL after cycle 6 blood draw
Exclusion Criteria:
* REGISTRATION (STEP 1): Any of the following prior therapies: Chemotherapy =\< 6 months prior to registration. NOTE: concurrent receipt of human epidermal growth factor receptor 2 (HER2) directed antibodies or antibody-drug conjugates, endocrine therapy, or cyclin-dependent kinase (CDK) 4/6 inhibitor is permitted
* REGISTRATION (STEP 1): Receiving any estrogen or progestin containing medications, including topical estrogens
* REGISTRATION (STEP 1): Planning to temporarily or permanently discontinue medical OFS in the next 12 months
Phase 1/2 Study of BHB810 in Advanced Gastric and GEJ Adenocarcinoma
BHB810 is an IV-administered investigational drug (mechanism not explicitly stated, though eligibility requires CDH17-positive tumors) being studied in Phase 1/2 for advanced/refractory gastric and gastroesophageal junction adenocarcinoma, with other CDH17-positive GI tumors (including colorectal and pancreatic) eligible in backfill/Phase 2 cohorts.
NCT07529808 · Phase 1/2 · BigHat Biosciences, Inc.
Recruiting sites: California, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
* Histologically confirmed advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has progressed on, was nonresponsive to, or for which no standard or available curative therapy exists.
* Participants in Phase 1 Backfill Cohorts \& Phase 2 must be CDH17-positive by central testing.
* Other gastrointestinal (GI) tumor types may be enrolled in Backfill Cohorts and Phase 2.
* At least 1 measurable target lesion at baseline per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
* Provision of FFPE archival tumor tissue. Additional fresh biopsies at screening are required in Phase 1 Backfill Cohorts and Phase 2.
* Adequate organ and marrow function as defined in the protocol
Exclusion Criteria:
* Prior cancer treatment as follows, relative to the first planned dose of trial intervention:
* Chemotherapy or targeted therapy withing 4 weeks or 5-halflives (whichever is shorter)
* Monoclonal antibody-based therapy (including ADCs) within 4 weeks
* Immune checkpoint inhibitors within 4 weeks
* Wide-field radiation therapy (\>30% marrow-bearing bones) within 4 weeks or \< 2 weeks of focal palliative radiation to nontarget lesions
* Prior treatment with a CDH17-directed therapy or an ADC with an auristatin (MMAE or MMAF)
* Known hypersensitivity or allergic reaction to BHB810 or it's excipients
* Left ventricular ejection fraction \<50% or history of congestive heart failure Class III/IV
* QTc interval \> 470 msec, history of risk factors for Torsade de Pointes, or taking a medication known to prolong QT/QTc
* Pregnant or breastfeeding females, or if you or your partner are planning to become pregnant
* Known or suspected brain metastases, leptomeningeal disease, or spinal cord compression. Participants with stable, treated brain metastases may be enrolled.
* Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or CYP3A4 sensitive substrate within 2 weeks of first dose of trial intervention
* Any condition that may compromise participant safety, compliance, or interfere with the evaluation of the study drug.
ProofPrincip IntraTu TCells SinglDoseImmunCheckpoinInhib Gastro-Esophage Adenocarcinoma w/ARID1a Mu
This trial gives a single-dose combination of the immune checkpoint inhibitors tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) to treatment-naïve, non-metastatic ARID1A-mutant esophageal, gastroesophageal junction, or gastric adenocarcinoma patients prior to definitive therapy.
NCT06824363 · Phase 1 · University of California, Irvine
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Non metastatic GEC including locally advanced unresectable
* Treatment naïve
* Histologically proven adenocarcinoma of the esophagus or the stomach with ARID1a mutation either by liquid biopsy (ctDNA) or tissue NGS/WES
* MSI-Stable or pMMR
* Age ≥ 18 years
* Body weight \> 66 pounds
* ECOG ≤ 2
* Repeat biopsy feasible
* No clinically significant autoimmune disease
Exclusion Criteria:
* Patients with known metastatic disease
* Prior systemic treatment for esophagus, GEJ, or the stomach adenocarcinoma
* Patients with uncontrolled autoimmune disease per investigator discretion
* Inability or refusal to undergo biopsy procedures to obtain tissue samples
Study of NTB-928 in R/R OC
NTB-928 is an investigational intravenous drug whose mechanism/target is not stated in the registry, being tested in a Phase 1 dose-escalation trial for adults with relapsed or refractory ovarian carcinoma who have already received standard treatments.
NCT07690189 · Phase 1 · TeneoSeven, Inc.
Recruiting sites: Alabama, Nebraska, New York, Texas
Read full eligibility criteria
Inclusion Criteria:
* Aged 18 years or older
* Have a confirmed diagnosis of ovarian cancer, including high-grade serous, high-grade endometrioid, low-grade serous, or clear cell ovarian cancer, or carcinosarcoma of the ovary. Patients with mucinous carcinoma are not eligible.
* Have relapsed or refractory ovarian cancer and have already received standard treatments known to provide benefit; participants are eligible if they have platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer (with clearly documented ineligibility for further platinum chemotherapy).
* Are able to understand the study requirements and are willing to provide written informed consent
* Are willing to use effective birth control during the study and for a period after the last dose of study treatment, if of childbearing potential
Exclusion Criteria:
* Have another active cancer that could interfere with assessment of this study treatment
* Have received another investigational drug or certain cancer treatments within a recent period before starting this study
* Are pregnant or breastfeeding
TCR1188-ABC Cells in KRAS-mutated Cancers
TCR1188-ABC cells, base-edited autologous T cells engineered to express TCR1188 and an anti-ILT4 (LILRB2) scFv, are being studied as a single infusion (following fludarabine/cyclophosphamide lymphodepletion and tocilizumab) in a Phase I dose-escalation trial for patients with KRAS G12V-mutated metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or NSCLC who have progressed after prior standard therapy.
NCT07594067 · Phase 1 · University of Pennsylvania
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
1. Patients ≥ 18 years of age
2. Patients with one of the following diagnoses:
1. Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma
2. Histologically confirmed metastatic colorectal cancer
3. Histologically confirmed metastatic non-small cell lung cancer
3. HLA-A\*11:01 positive as confirmed by a CLIA certified laboratory.
4. KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.
5. Received prior treatment for their primary malignancy as follows:
1. Pancreatic Cancer/Cholangiocarcinoma Patients: At least one prior line of standard of care therapy for advanced stage disease. For pancreatic cancer patients, this must include a gemcitabine or fluorouracil (5 FU)-based regimen.
2. Colorectal Cancer Patients: At least three prior lines of standard of care therapy for advanced stage disease. Prior treatment must include all of the following unless the patient was ineligible for a specific therapy type: i). a fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimen, ii). an anti-vascular endothelial growth factor (VEGF) agent, and iii). regorafenib, trifluridine-tipiracil, or fruquintinib. Patients with microsatellite instability-high (MSI-H) disease must also have received, or be ineligible for, prior treatment with an immune checkpoint inhibitor.
3. Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.
6. Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.
7. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:
1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
2. ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
3. Total bilirubin ≤ 1.5 mg/dL x ULN, unless the subject has Gilbert's syndrome (if so, direct bilirubin must be ≤ 2.0 mg/dL x ULN)
4. Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO/MUGA
5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
8. Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:
1. Hemoglobin ≥ 8 g/dL
2. Absolute neutrophil count ≥ 1000/μL
3. Platelet count ≥ 100,000/μL
9. ECOG Performance Status that is either 0 or 1.
10. Signed, written informed consent
Exclusion Criteria:
1. Active hepatitis B or hepatitis C infection
2. Patients with a severe acquired or inherited immunodeficiency, including HIV positive patients with a CD4 count ≤ 350 cells/μL. In order to qualify, HIV positive patients must also be on an established antiretroviral therapy regimen with a viral load of \<400 copies/mL.
3. Any other active, uncontrolled infection.
4. Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5).
5. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
6. Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
7. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.
8. Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.6.
9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
10. Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and/or myocardial infarction within 6 months of physician-investigator confirmation of eligibility.
11. Prior history of myocarditis.
12. Patients with pneumonitis/interstitial lung disease requiring steroid treatment.
13. Patients with active/untreated brain metastases. \[Note: History of treated metastases may still be eligible.\]
14. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.
177Lu-BetaBart in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors
177Lu-BetaBart, a lutetium-177-labeled anti-B7-H3 monoclonal antibody radioimmunoconjugate, is being studied in a phase 1/2a dose-escalation and expansion trial for patients with relapsed/refractory, locally advanced inoperable, or metastatic solid tumors including CRPC, colorectal, NSCLC/SCLC, ovarian, cervical, endometrial, TNBC, HNSCC, and esophageal squamous cell carcinoma who have progressed on prior standard therapy.
NCT07189871 · Phase 1/2 · Radiopharm Theranostics, Ltd
Recruiting sites: Alabama, Michigan, Nebraska, Texas
Read full eligibility criteria
1. Participants ≥ 18 years of age.
2. Participants with a documented history of histopathologically confirmed CRPC\*, CRC, NSCLC, SCLC, HNSCC, ovarian cancer, cervical cancer, endometrial cancer, TNBC, or ESCC.
a. \*Progressive CRPC defined by at least one of the following criteria: i. Two consecutive increases in PSA measured at least 1 week apart. ii. Soft tissue progression defined as a ≥20% increase in the sum of the diameter or the appearance of one or more new lesions by computed tomography (CT)/magnetic resonance imaging (MRI).
iii. Progression of bone disease defined by Prostate Cancer Working Group 3 (PCWG3) as evaluable disease or new bone lesions by bone scan.
iv. Identification of new soft tissue or bone lesions on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
b. \*Metastatic disease defined as either or both of the following: i. Documented M1 disease on conventional imaging ii. Identification of bone lesion(s), extra-pelvic soft tissue lesion(s), or visceral metastases on PSMA PET imaging with an FDA-approved imaging agent c. \*Progression following treatment with ADT and at least one ARSI . e. Participants with liver metastases if they meet the following criteria: i. ≤3 lesions ii. All lesions must be ≤2 cm in the short axis iii. SUVmean ≥2 x that of liver parenchyma g. Participants with TNBC if pathology results confirm the following: i. Estrogen receptor expression \<1%, ii. Progesterone receptor expression \<1%, iii. Human epidermal growth factor receptor 2 (HER2) negative, defined as IHC 0 or 1+, or IHC 2+ with negative in situ hybridization (ISH)
3. Participants must have documented disease progression during or after their most recent line of anticancer therapy. Participants must be refractory to or intolerant of standard of care therapy or have no standard of care therapy available that is likely to provide clinical benefit.
4. Must have at least 1 measurable target lesion according to RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Participants must have a life expectancy of ≥ 4 months in the opinion of the Investigator.
7. Participants of child-bearing potential (CBP) must have a negative β-hCG test and must not be breastfeeding.
8. Participants of CBP must agree to use a highly effective method of contraception.
9. Participants with previously treated brain metastases are eligible to participate if:
* they are neurologically and radiologically stable for at least 28 days prior to the first dose of 177Lu-BetaBart; and
* have no history of leptomeningeal disease or spinal cord compression.
Exclusion Criteria:
1. History of prior organ transplant.
2. Any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer.
3. Have any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures.
4. Residual toxicity ≥ Grade 2 from prior anti-cancer therapy
5. History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics.
6. Inadequate organ functions as reflected in laboratory parameters:
* Estimated glomerular filtration rate (eGFR) \< 50 mL/min
* Platelet count of \< 100 x 109/L
* Absolute neutrophil count (ANC) \< 1.5 x 109/L
* Hemoglobin \< 9 g/dL
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 x upper limit of normal (ULN), or \> 5 x ULN for participants with known liver metastases
* Total bilirubin \> 1.5 x ULN
7. Participants requiring blood product transfusion within 2 weeks of first dose of 177Lu-BetaBart.
8. \*Participants with CRPC who have received prior Lu-177-PSMA radioligand therapy.
9. Clinically significant cardiovascular disease
10. Participation in any other interventional investigational trial
11. Participants who are pregnant or breastfeeding.
12. Major surgery within 4 weeks prior to first dose of 177Lu-BetaBart.
13. Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, ≤ 28 days prior to the first dose of 177Lu-BetaBart.
14. Known active hepatitis B or known active hepatitis C infection.
15. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s)
16. Untreated moderate to severe hydronephrosis
17. For CRPC participants, prescence of a superscan by nuclear medicine/99mTc bone scan.
18. Active autoimmune disease that has required systemic treatment within 90 days.
19. Any other clinically significant comorbidities, which in the judgment of the investigator could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the subject to safety risks.
177Lu-DOTATATE Modified Delivery Based on Individualized Dosimetry
Lutetium Lu 177 dotatate (Lutathera), a somatostatin receptor-targeted radiopharmaceutical, is being studied with individualized dosimetry-based dosing versus standard FDA-approved dosing in adults with unresectable/metastatic gastroenteropancreatic neuroendocrine tumors.
NCT06395402 · Phase 2 · University of Iowa
Recruiting sites: Iowa
Read full eligibility criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria. A physical, with vital signs, concomitant medication review, and medical history must be completed within 60 calendar days to confirm appropriateness of Lutathera treatment as well as to foundation for listed criteria.
Inclusion Criteria:
* Provision of signed and dated informed consent form.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Aged ≥ 18 years at time of consent.
* Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be a well-differentiated neuroendocrine tumor (Ki-67 ≤ 20%) with the primary tumor location known or believed to be gastroenteropancreatic origin (GEP-NET)
* Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST that shows uptake \> liver background on sstr2 PET/CT with any FDA approved sstr2 imaging agent. SSTR2 PET/CT must have been obtained within 90 days prior to scheduled C1D1 of Lutathera.
* Recommended to receive LUTATHERA® therapy for unresectable and/or metastatic neuroendocrine disease.
* Adequate performance status (ECOG of 0 or 1; or Karnofsky performance status of ≥70).
* Agrees to contraception during therapy.
* Neutrophil count within normal limits within 28 days of treatment day 1.
* Platelet count within normal limits within 28 days of treatment day 1.
* Ability to take oral medication and be willing to adhere to the treatment regimen
* For individuals of reproductive potential: agreement to use effective birth control
* Agreement to adhere to Lifestyle Considerations throughout study duration: abstain from caffeine or xanthine-containing products as well as alcohol before the start of cycle dosing and through the cycle's final blood sample; minimize social interactions during low blood counts.
Exclusion Criteria:
* Individuals who are pregnant or lactating (note: potential participants should not engage in 'pump \& dump' strategy; lactation must be discontinued).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring inpatient admission or a delay to start of therapy), fever, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Surgery, radiation therapy, or chemotherapy ≤ 4 weeks of C1D1 (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).
* Prior peptide-receptor radiotherapy (PRRT).
* Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable).
* A concurrent malignancy that, in the opinion of the investigator, would cause a safety risk by delaying therapy or confound/negatively impact study objectives (documentation of the rationale must be provided)
* Prior external beam radiation dose to the kidneys of \>10 Gy (mean dose to functional renal volume).
* Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of ≤ 5 Gy) as estimated by a radiation oncologist.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Octreoscan® or Netspot™.
177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer
177Lu-DOTATATE, a somatostatin receptor 2-targeted radioconjugate delivering beta-emitting lutetium-177, is being studied in SSTR-positive stage IV or recurrent metastatic breast cancer after prior standard therapies.
NCT04529044 · Phase 2 · OHSU Knight Cancer Institute
Recruiting sites: Oregon
Read full eligibility criteria
Inclusion Criteria:
* Life expectancy of \> 6 months, as determined by the investigator
* Ability to understand and the willingness to sign a written informed consent document
* Patients aged \>= 18-100 years old at time of informed consent
* Histologically or cytologically confirmed metastatic breast carcinoma
* Stage IV or recurrent disease with distant metastases
* Female and male patients with breast cancer will be included in the study
* Participants must have experienced disease progression after at least two lines of standard treatment modalities and/or one prior line of cytotoxic chemotherapy (not just endocrine therapy). Specifically, patients must have received or declined the following therapies: a) Hormone receptor positive (HR+)/HER2: endocrine therapy and CDK4/6 inhibitor (i); b) HER2+: trastuzumab, pertuzumab, T-DM1 and tucatinib; c) Triple negative breast cancer (TNBC): chemotherapy, immunotherapy (in PD-L1+ tumors). Patients can be consented if they are foregoing treatments known to confer survival advantage
* Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v1).1 that is amendable to biopsy
* Confirmed presence of SSTR based on \> 50% of lesions with DOTATATE uptake of 68Ga DOTATATE equivalent to the liver
* Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia and =\< grade 2 neuropathy which are allowed
* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Participant must consent to undergo a pre-treatment screening biopsy for enrollment
* Hemoglobin \>= 8.0 g/dL with no blood transfusion in the past 28 days (measured within 28 days prior to administration of study treatment)
* Absolute neutrophil count (ANC) \>= 2.0 x 10\^9/L (measured within 28 days prior to administration of study treatment)
* Platelet count \>= 75 x 10\^9/L (measured within 28 days prior to administration of study treatment)
* Total bilirubin =\< 3 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (unless liver metastases are present in which case they must be =\< 5 x ULN) (measured within 28 days prior to administration of study treatment)
* Serum albumin \>= 3.0 g/L, unless prothrombin time or international normalized ratio (INR) value is within the normal range (measured within 28 days prior to administration of study treatment)
* Participants must have serum creatinine =\< 1.7 mg/dL, or creatinine clearance estimated of \>= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment)
* Female participants of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* FOCBP agree to use a highly-effective method of contraception starting with the first dose of study therapy up to 7 months after the last dose of study therapy
* FOCBP are those who are not proven postmenopausal. Postmenopausal is defined as:
* Amenorrheic for \> 24 consecutive months following cessation of exogenous hormonal treatments
* Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 years of age
* Radiation-induced oophorectomy with last menses \> 1 year ago
* Chemotherapy-induced menopause with \> 1 year interval since last menses
* Surgical sterilization (bilateral oophorectomy or hysterectomy or tubal ligation)
Exclusion Criteria:
* Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of first dose of 177Lu- DOTATATE treatment
* Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device
* Prior external beam radiation therapy to more than 25% of the bone marrow
* Other malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer or curatively treated in situ cancer of the cervix
* Known brain metastases, unless these metastases have been treated and stabilized
* Peptide receptor radionuclide therapy at any time prior to study enrollment
* Known hypersensitivity to somatostatin analogues or any component of the 68Ga- DOTATATE or 177Lu- DOTATATE formulations
* Patients with uncontrolled infection will not be enrolled until infection is treated per provider discretion
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
* Uncontrolled diabetes mellitus as defined by a fasting blood glucose \> 2x ULN
* Any patient receiving treatment with short-acting somatostatin analogs, which cannot be interrupted for both 24 hours before and after the administration of 177Lu, or any patient receiving treatment with long-acting release somatostatin analogs that cannot be interrupted for at least 4 weeks before the administration of 177Lu- DOTATATE
* Any surgery or radiofrequency ablation within 12 weeks prior to enrollment in the study; or prior radioembolization; chemoembolization; or external beam radiation therapy (EBRT) to \> 25% of bone marrow, at any time
* Any chemotherapy or targeted therapy within 4 weeks prior to enrollment in the study
* Current spontaneous urinary incontinence making impossible the safe administration of the radioactive study agent
* Any psychiatric illness that prevents patient from informed consent process
* Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
* Participant is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment
177Lu-PSMA-617 With Liver Directed Therapy in Metastatic Castration Resistant Prostate Cancer
177Lu-PSMA-617, a PSMA-targeted radioligand therapy delivering beta radiation to PSMA-expressing cells, is combined with liver-directed therapy (ablation or TACE) in metastatic castration-resistant prostate cancer patients with liver metastases who progressed on prior androgen pathway inhibitors.
NCT07145177 · Phase 1 · University of California, San Francisco
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed prostate cancer.
2. Progressive disease by PCWG3 criteria at study entry.
3. Male participants who are at least 18 years of age on the day of signing informed consent.
4. Castrate level of serum testosterone at study entry (\< 50 ng/dL). Note: Participants without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study treatment.
5. Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide.
6. Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must have recovered to Grade ≤ 1 (except for any grade alopecia and grade ≤ 2 neuropathy).
7. Prior external beam radiotherapy is allowed if the last radiotherapy treatment was greater than 2 weeks from start of study treatment on Cycle 1 Day 1 (C1D1). Note: Participants must have recovered from all radiation-related toxicities. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
8. At least one PSMA-avid extrahepatic lesion on screening PSMA Positron Emission Tomography (PET). A positive lesion is defined as uptake above background liver. Hepatic lesions may be PSMA PETnegative or positive.
9. Availability of archival mCRPC tissue, or presence of a metastatic lesion that is amenable to fresh biopsy and willingness to undergo biopsy during screening if no archival mCRPC tissue available.
10. The presence of one or more liver metastases amenable to liver-directed therapy in the judgment of the treating interventional radiologist. Liver metastases may be detected by CT or magnetic resonance imaging (MRI), and biopsy confirmation is not required.
11. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky ≥ 50%.
12. Demonstrates adequate organ function as defined below:
1. Absolute neutrophil count ≥ 1,500/ microliter (mcL).
2. Platelets ≥ 100,000/mcL.
3. Hemoglobin \> 9.0 g/dL.
4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN). In participants with known or suspected Gilbert's disease, direct bilirubin ≤ ULN.
5. aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 5 x institutional upper limit of normal.
6. alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 5 x institutional upper limit of normal.
7. Prothrombin time ≤ 1.5 x institutional upper limit of normal (unless on medical therapy known to prolong prothrombin time).
8. Albumin ≥ 2.8 g/dL
9. Creatinine clearance Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2, calculated using the Cockcroft-Gault equation or 24 hour urine collection.
13. Participants with previously treated brain metastases are eligible provided the following criteria are all met:
1. Last treatment was \> 28 days prior to C1D1
2. No evidence of new/progressive brain metastases is observed on MRI obtained during the Screening window
14. Participants must use appropriate methods of contraception during study treatment and for at least 6 months after last study treatment. Note: Participants who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea \> 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential. Participants who have undergone vasectomy themselves should also be considered to be of childbearing potential. Acceptable methods of contraception include continuous total abstinence, or double barrier method of birth control (e.g., condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception.
15. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. De novo small cell neuroendocrine prostate cancer.
2. One or more extrahepatic soft tissue lesions (lymph nodes \> 1.5 cm in short axis, visceral/soft tissue lesions \> 1 cm) on screening CT that is negative on PSMA PET. Non- PSMA avid liver lesions are allowed.
3. Recipient of other systemic anti-cancer therapies administered within 14 days, or 5 half lives, whichever is shorter, prior to initiation of study treatment. Note: LHRH analogues are the exception and are permitted
4. Recipient of prior PSMA-directed radioligand treatment.
5. Recipient of \> 2 lines of prior taxane-based chemotherapy administered in the castration-resistant setting. Prior taxane in the castration sensitive setting does not count towards this limit. If platinum chemotherapy is added to taxane this does not count as a separate line of treatment.
6. Previous bilio-enteric anastomosis, ampulla of Vater sphincterotomy, biliary stent, or biliary drain passing through the ampulla of Vater.
7. Currently participating in a study of an investigational therapeutic agent or has used an investigational device within 4 weeks prior to the first dose of study treatment on C1D1. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
8. Clinically significant cardiovascular disease including, but not limited to:
1. Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure.
2. Uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months before study entry.
3. Clinically significant arrhythmias not controlled by medication. Note: Chronic rate-controlled or paroxysmal atrial fibrillation/flutter is not an exclusion to study participation.
9. Major surgery within 28 days of study treatment. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment on C1D1. Minor procedures (e.g., biopsy, cataract surgery, stent placement, endoscopy) are not considered major surgery.
10. Has a secondary malignancy requiring active treatment at study entry (except for carcinoma-in-situ, non-muscle invasive bladder cancer, and non-melanoma skin cancer).
11. Has an active infection requiring intravenous antibiotics within 7 days prior to C1D1.
12. Has a known history of Hepatitis B infection (Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus infection (HCV RNA \[qualitative\] detected, with the following exceptions:
1. Participants who are HbsAg positive are eligible if they have received hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study entry.
2. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to study entry.
13. Not a candidate for liver-directed therapy on the basis of any of the following:
1. History of bleeding diathesis and currently on anti-coagulation therapy that cannot be safely discontinued for liver directed therapy.
2. Clinically significant ascites including requiring more than one paracentesis in the 28 days prior to C1D1.
14. Unable or unwilling to follow radiation safety precautions following each dose of radioligand therapy or liver directed therapy.
15. Any condition that, in the opinion of the Principal Investigator, would impair the participant's ability to comply with study procedures.
177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer
This phase 1 trial tests the PSMA-targeted radioligand therapy 177Lu-PSMA-617 combined with the cellular immunotherapy/vaccine sipuleucel-T versus 177Lu-PSMA-617 alone in patients with metastatic castration-resistant prostate cancer.
NCT07219147 · Phase 1 · City of Hope Medical Center
Recruiting sites: California
Read full eligibility criteria
Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies
* If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 1
* Male
* Progressive castration-resistant metastatic prostate cancer with pathologically confirmed adenocarcinoma of the prostate without small cell features
* Patients must have either:
* Measurable disease
* For extranodal (visceral) lesions (e.g. lung, liver, etc.) to be considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT
* For lymph nodes to be considered measurable (i.e., target or evaluable lesions), they must be ≥ 20 mm in at least one dimension, using spiral CT
* OR non-measurable disease
* All other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan) and truly non-measurable lesions
* Lesions that are considered non-measurable include bone lesions (only). Progression on first generation ADT
* Patients must have been on androgen deprivation therapy with a gonadotrophin releasing hormone (GnRH) analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration) for at least 3 months prior to study entry and maintain castrate levels of serum testosterone \< 50 ng/dL throughout study participation unless intolerant
* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (within 10 days prior to day 1 of protocol therapy)
* White blood cell (WBC) counts \> 2500/uL (within 10 days prior to day 1 of protocol therapy)
* Lymphocyte count ≥ 300/uL (within 10 days prior to day 1 of protocol therapy)
* Platelets ≥ 100,000/mm\^3 (within 10 days prior to day 1 of protocol therapy)
* Hemoglobin ≥ 9g/dL (within 10 days prior to day 1 of protocol therapy)
* NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 10 days prior to day 1 of protocol therapy) (unless has Gilbert's disease, serum bilirubin level ≤ 3 x ULN)
* Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 10 days prior to day 1 of protocol therapy)
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN (within 10 days prior to day 1 of protocol therapy)
* Alkaline phosphatase ≤ 3 x ULN (within 10 days prior to day 1 of protocol therapy) (Patients with documented bone metastases, alkaline phosphatase \[ALP\] ≤ 5 x ULN)
* Serum creatinine ≤ 1.5 x ULN or creatinine clearance of ≥ 50 mL/min per Cockcroft-Gault formula (within 10 days prior to day 1 of protocol therapy)
* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (within 10 days prior to day 1 of protocol therapy)
* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (within 10 days prior to day 1 of protocol therapy)
* If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.3 x ULN (within 10 days prior to day 1 of protocol therapy)
* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (within 10 days prior to day 1 of protocol therapy)
* Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\]) (within 10 days prior to day 1 of protocol therapy)
* If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed. OR
* If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
* Meets other institutional and federal requirements for infectious disease titer requirements
* Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
* For male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion Criteria:
* Any approved or investigational anticancer therapy, including chemotherapy, hormonal therapy (e.g., androgen receptor \[AR\] antagonists, 5 alpha reductase inhibitor, estrogen), or radiotherapy, within 4 weeks prior to initiation of study treatment
* Treatment with any of the following medications or interventions within 28 days of registration:
* External beam radiation therapy or surgery
* Chrysanthemum morifolium/Ganoderma lucidum/Glycyrrhiza glabra/Isatis indigotica/Panax pseudoginseng/Rabdosia rubescens/Scutellaria baicalensis/Serona repens supplement (PC-SPES) (or PC-SPEC) or saw palmetto
* Systemic corticosteroids. Use of inhaled, intranasal, and topical steroids is acceptable
* Megestrol acetate (Megace®), diethyl stilbestrol (DES), or cyproterone acetate
* Ketoconazole
* 5-alpha-reductase inhibitors (e.g., finasteride \[Proscar®\], dutasteride \[Avodart®\])
* High dose calcitriol (1,25\[OH\]2 vitamin \[Vit\]D) (i.e., \> 7.0 ug/week)
* Prior treatment with 177\^Lu-PSMA-617 and/or sipuleucel-T
* Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
* Treatment with any investigational vaccine within 2 years of registration or treatment with any other investigational product within 28 days of registration
* Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
* Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
* Inability to comply with study and follow-up procedures
* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
24BRO681 : Alternating Gnp and mFOLFIRINOX for BR-PDAC
This trial studies alternating neoadjuvant chemotherapy regimens—nab-paclitaxel plus gemcitabine alternating with modified FOLFIRINOX—in patients with borderline resectable pancreatic adenocarcinoma prior to surgery.
NCT07043270 · Phase 2 · Dartmouth-Hitchcock Medical Center
Recruiting sites: New Hampshire
Read full eligibility criteria
Inclusion Criteria:
* Age ≥ 18 years
* Diagnosis of BR-PDAC. The resectability should be officially determined with surgical oncologists at the Dartmouth Cancer Center (DCC) GI multidisciplinary Tumor Board based on NCCN Guidelines Version 2.2024 Pancreatic Adenocarcinoma.
* Patients must be able and willing to provide informed consent.
* Contrast-enhanced CT scan of the chest, abdomen, and pelvis performed within 45 days before registration.
* ECOG Performance Status: 0-1.
* Females of childbearing potential must have a negative pregnancy test done ≤ 14 days prior to study enrollment, and must agree to use a highly effective method of contraception throughout the course of protocol therapy.
Exclusion Criteria:
* Any prior receipt of chemotherapy or radiation therapy for PDAC.
* Known DPYD poor metabolizer genotype.
* Known BRCA1/2 or PALB2 mutations. If they are found to have BRCA1/2 or PALB2 mutation after inclusion to the trial, the participant will be taken off of protocol therapy (since platinum-containing therapy is preferred for these patients).
* Any confirmed second malignancy that is likely to require systemic therapy during the study period, in the opinion of the enrolling investigator.
* Any of the following baseline laboratory abnormalities:
* Absolute neutrophil count (ANC) \< 2,500/mm3
* Platelet count \< 100,000/mm3
* Hemoglobin \< 7 g/dL
* Creatinine \> 1.5 x upper limit of normal (ULN)
* Total bilirubin \> 1.5 x ULN
* AST/ALT \> 5 x ULN
* Any peripheral sensory neuropathy that meaningfully impairs performance of instrumental activities of daily living, as evaluated by the enrolling investigator.
* Patients who are unable to provide informed consent.
* Patients who are pregnant or breastfeeding.
* Patients who are incarcerated.
3-5 FrAction Stereotactic Body Radiation Therapy for Palliation of Head and Neck Squamous Cell Carcinoma: the FAST Phase II Randomized Trial
This trial randomizes patients with head and neck squamous cell carcinoma who are ineligible for curative-intent treatment to receive either short-course (3-5 fraction) stereotactic body radiotherapy or traditional palliative radiotherapy.
NCT05674396 · Phase 2 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
* Age 18 or older
* Willing to provide informed consent
* Histologically confirmed squamous cell carcinoma
* Primary tumor site in the head and neck (includes oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, salivary gland, and cutaneous subsites as well as tumors of unknown primary site)
* Ineligible for curative intent treatment after multidisciplinary evaluation (including evaluation by radiation oncologist and surgeon followed by presentation at multidisciplinary tumor board prior to randomization)
* Prior therapy including radiation, surgery, or systemic therapy is permitted unless further radiation is deemed inappropriate by the enrolling physician
* Metastatic disease is permitted
Exclusion Criteria:
* Contraindications to radiotherapy
* Pregnant or lactating women
5.0 PRE-TREATMENT EVALUATION
* History and physical examination including laryngopharyngoscopy by a radiation oncologist and/or head and neck surgeon within 8 weeks prior to randomization.
o Clinical examination will include a detailed description of disease target including measurement where feasible to facilitate response assessment
* Documentation of smoking history
* Staging imaging within 12 weeks prior to randomization:
* Contrast-enhanced CT of the neck and chest or
* MRI of the neck with CT of the chest or
* Whole body PET/CT
* Histological confirmation of squamous cell carcinoma
* Pregnancy test for women of child-bearing age, within 2 weeks prior to randomization
* Assessment of all baseline symptoms, using CTCAE version 5.0 within 2 weeks prior to randomization.
* Assessment of baseline pain score (NRS) and analgesic use (non-opioid and opioid)
* Completion of QOL scoring within 2 weeks of randomization
* Informed consents must be obtained prior to any study specific activities
5 vs. 9-day Course of Whole Breast Radiotherapy With Boost for Early-stage Breast Cancer
This trial compares a 5-day versus 9-day hypofractionated whole breast radiotherapy schedule with boost following lumpectomy in early-stage invasive breast cancer or DCIS.
NCT06961955 · Phase 2 · University of Utah
Recruiting sites: Utah
Read full eligibility criteria
Inclusion Criteria:
* Female participant aged ≥ 18 years.
--Participants must have at least one of the following risk factors:
* Grade 3 invasive histology
* Estrogen receptor positivity less than 5%
* Lymphovascular invasion
* Invasive margins \<2mm on surgical pathology
* DCIS final positive margin
* Extensive intraductal component
* Age ≤ 50 years
* Tumor size \> 2 cm
* Histologically confirmed invasive carcinoma or Ductal Carcinoma In Situ (DCIS) of the breast.
* Breast cancer stage (AJCC v8) T0-3, N0, M0. T0 N0 is allowed if whole breast radiation is recommended by the treating physician.
* Lumpectomy within 84 days of the start of radiation.
* ECOG Performance Status ≤ 2, or KPS ≥ 50
* Negative inked histologic margins from lumpectomy, with the exception of a focus of positive margin at the pectoralis fascia.
* Negative pregnancy test for participants of childbearing potential, evidence of permanent surgical sterilization, or post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* \< 50 years of age:
* Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
* Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
* ≥ 50 years of age:
* Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
* Had radiation-induced menopause with last menses \>1 year ago; or
* Had chemotherapy-induced menopause with last menses \>1 year ago
* Sexually active participants of childbearing potential must agree to use highly effective method of contraception (defined in Section 5.4.1) during the course of radiation and for 30 days after radiation.
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
* Bilateral breast cancer.
* Prior radiation therapy to the chest.
* Prior chemotherapy.
* Recurrent disease.
* Known metastases or node positive.
* Major chest surgery which is expected to impact study participation 8 weeks prior to starting study drug.
* Prior breast malignancy in either breast.
* The diagnosis of any other malignancy which, in the opinion of the Investigator, is likely to negatively impact the subject's safety or ability to participate in the study.
* Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
* Cardiovascular disorders:
* Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
* Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
* Any other condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow, social/ psychological issues, etc.)
* Significant post lumpectomy complications requiring an unplanned re-operation for surgical complications or admission for IV antibiotics. Re-operation for margins evaluation or nodal evaluation is acceptable. Draining of a seroma is not considered a complication unless it has become infected.
* Breast neuroendocrine carcinoma or sarcoma histology.
* Radiation sensitizing disease or condition (e.g. connective tissue disease, li fremani, etc.).
* Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
* Participants receiving concurrent radiation sensitizing medications or therapies.
5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC
This trial studies 5-azacytidine, a demethylating agent, combined with or compared to nivolumab, a PD-1 immune checkpoint inhibitor, in patients with resectable HPV-associated oropharyngeal squamous cell carcinoma prior to surgery.
NCT05317000 · Phase 2 · Barbara Burtness
Recruiting sites: Connecticut
Read full eligibility criteria
Inclusion Criteria:
1. Patients with resectable squamous cell carcinoma of the oropharynx. Histologic or cytologic confirmation from either a biopsy/aspirate of the oropharyngeal primary lesion and/or a regional lymph node is required.
2. T1-T3, N0-N2, M0 stage by AJCC 8th edition for HPV-initiated oropharynx cancer.
3. Resectability confirmed by a surgical co-investigator; evaluation may include operative endoscopy to discover second primaries and map tumor extent with biopsy
4. In addition to diagnostic biopsies, biopsies in clinic or at the time of operative endoscopy are required to yield primary tumor for research purposes \> 3mm cup forceps biopsies X 3. Prior biopsies for research obtained with informed consent for the Yale Biosample Repository Protocol are acceptable if they meet the volume requirements above.
5. HPV-association confirmed by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells).
6. Age \> 18 years. 5-azacytidine and nivolumab are tolerated in the elderly and there is no upper age limit for patients with adequate performance status.
7. ECOG performance status 0 or 1.
8. Absolute neutrophil count (ANC) \> 1500/microliter, absolute lymphocyte count (ALC) \> 1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter.
9. AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
10. Albumin \> 3.0 g/dl.
11. Creatinine \< 1.5 x upper limit of normal.
12. Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window.
13. Willing and able to provide written informed consent. Informed consent is required prior to research-related activities, including biopsy. However, if written informed consent for participation in the biosample repository protocol has been obtained, tissue obtained under that consent can be used to meet eligibility criterion
Exclusion Criteria:
1. Medical contraindication to transoral surgery.
2. Full dose anticoagulation.
3. Concomitant invasive malignancy, or malignancy within 2 years except for hormonally responsive breast or prostate cancer, resected non-melanoma skin cancer, resected uterine cervical carcinoma or meningioma.
4. Inability to give informed consent.
5. Prior systemic therapy, radiation, or gross resection for the tumor under study.
6. Women may not be pregnant or breast-feeding.
7. Patients with active autoimmune disease, supraphysiologic systemic corticosteroid use within 7 days, and/or allergies/contraindications to the study drugs are excluded.
5-Fluorouracil Response and Optimization STudy (The FROST Trial)
This phase II trial compares two dosing schedules of the antimetabolite chemotherapy 5-fluorouracil as second-line-or-later treatment for recurrent/metastatic head and neck squamous cell carcinoma after prior platinum and PD-1 inhibitor therapy.
NCT07419464 · Phase 2 · Washington University School of Medicine
Recruiting sites: Missouri
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically confirmed:
* RM-HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx, OR
* p16+ (HPV-related) level 2-3 neck node and unknown primary site, OR
* Second primary HNSCC in a previously radiated field not amenable to curative-intent surgery and/or re-radiation.
* Measurable disease per RECIST 1.1.
* Previously treated with platinum-based chemotherapy, RM disease within 6 months of definitive cisplatin + radiation therapy (DCisRT) or post-operative adjuvant cisplatin + radiation therapy (POACisRT) OR progressive disease on or after or intolerance to platinum agent given for RM disease.
* Previously treated with PD-1 inhibitor, RM disease within 6 months of PD-1 inhibitor given as part of curative-intent therapy OR progressive disease on or after PD-1 inhibitor given for RM disease OR intolerance to prior PD-1 inhibitor in the curative or metastatic setting.
* At least 18 years of age
* ECOG performance status ≤ 2
* Adequate bone marrow and organ function as defined below:
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 100 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3 x IULN)
* AST(SGOT)/ALT(SGPT)/Alkaline Phosphatase (ALP) ≤ 3.0 x IULN. For subjects with documented bone metastasis, ALP ≤ 5.0 x IULN.
* Serum creatinine \<3 mg/dL or creatinine clearance \> 30 mL/min by Cockcroft- Gault.
* The effects of 5-FU on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after last dose of 5-FU
* Recovery to baseline or ≤ grade 1 from AEs due to prior therapy, unless AEs are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, or ≤ grade 2 neuropathy are permitted.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* Prior 5-FU given to treat RM-HNSCC.
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
* Currently receiving any other investigational agents.
* RM or incurable second primary SCC of cutaneous, nasopharynx, paranasal/nasal/sinus origin.
* DPYD deficiency (poor or intermediate metabolizer) as determined by next generation sequencing through blood or saliva (results of historical testing are accepted).
* Severe hepatic impairment (Child-Pugh C) or history of hepatitis B or C.
* Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-FU or other agents used in the study.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 14 days of study registration.
* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer
This phase 2 trial compares 5-fluorouracil/leucovorin combined with regorafenib (an oral multikinase inhibitor of VEGFR2/3, RET, KIT, PDGFR, and Raf) against trifluridine-tipiracil plus bevacizumab in third-line treatment of metastatic colorectal cancer.
NCT06887218 · Phase 2 · The Methodist Hospital Research Institute
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Male or female ≥18 years of age.
2. Histopathological or cytologically confirmed metastatic CRC.
3. Failed second-line therapy for metastatic disease.
4. A minimum of one measurable disease per RECISTv1.1.
5. ECOG performance status of 0-2.
6. Life expectancy ≥6 months per treating physician or principal investigator.
7. Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
8. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
a. Total bilirubin ≤ 10 x the upper limits of normal (ULN) b. Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) c. Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) d. Serum creatinine ≤ 1.5 x the ULN e. International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x ULN. (Subjects who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.
f. Platelet count ≥100000 /mm3, hemoglobin (Hb) ≥9 g/dL, absolute neutrophil count (ANC) ≥1500/mm3. Blood transfusion to meet the inclusion criteria will not be allowed.
9. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the investigator.
10. Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 2 months after the last dose of study drug as outlined in Appendices 12.2
11. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
12. Subject must be able to swallow and retain oral medication.
Exclusion Criteria:
* 1\. Hematology laboratory values of:
1. Absolute neutrophil count ≤1000 cells/mm3
2. Platelets ≤70,000 cells/mm3
3. Hemoglobin ≤9 g/dL
4. White blood count ≤3000 cells/mm3. 2. Hepatic laboratory values of aspartate transaminase or alanine aminotransferase:
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1. \>5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
2. \>2.5 × ULN if no liver metastases are present. 3. Serum albumin \<5.8 g/dL. 4. Total bilirubin \>10 mg/dL. 5. Prothrombin time (PT) or international normalized ratio (INR) \>1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
6\. Serum creatinine or serum urea \>1.5 × ULN. 7. Estimated glomerular filtration rate \<50 mL/min. 8. Positive pregnancy test, pregnant, or breastfeeding (female patients only). 9. Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study.
10\. Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to:
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1. Arrhythmia
2. Bradycardia
3. Tachycardia
4. Symptomatic valvular disease
5. Symptomatic congestive heart failure is classified by New York Heart Association as Class III or IV
6. Unstable angina pectoris. 11. Myocardial infarction within the past 6 months from the consent date. 12. Active bleeding diathesis. 13. Current complaints of persistent constipation or history of chronic constipation, bowel obstruction, or fecaloma within the past 6 months from the consent date.
14\. Known history and/or uncontrolled hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV)-1 or HIV-2 from the consent date.
15\. Active or recent (within 3 years) non-colorectal cancer malignancies, except for low-risk, cured cancers (e.g., squamous or basal cell carcinomas, in situ carcinomas, or others deemed non-significant by the investigator).
16\. Receipt of live, attenuated vaccine (e.g., intranasal influenza, measles, mumps, rubella, varicella) or close contact with someone who has received a live, attenuated vaccine within the past 1 month. Note: Influenza vaccine will be allowed if administered \>21 days.
17\. Receipt of any investigation agent or study treatment within the past 30 days.
18\. Ongoing infection \> Grade 2 NCI-CTCAE V5.0. 19. Symptomatic metastatic brain or meningeal tumors. 20. The presence of a non-healing wound, non-healing ulcer, or bone fracture. 21. Major surgical procedure or significant traumatic injury within 28 days before start of study medication 22. Renal failure that requires hemo-or peritoneal dialysis.
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1. Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
23\. Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE V5.0\] on repeated measurement) despite optimal medical management.
24\. Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
25\. Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment within 6 months of informed consent.
26\. Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed. All cancer treatments must be completed at least 3 years prior to registration.
27\. Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea).
28\. Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.
29\. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
30\. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)
67Cu-SAR-bisPSMA is a PSMA-targeted radioligand therapy delivering beta radiation to PSMA-expressing tumor cells, studied (with 64Cu-SAR-bisPSMA PET/CT for lesion selection) in patients with metastatic castration-resistant prostate cancer who have progressed on prior androgen receptor pathway inhibitor therapy.
NCT04868604 · Phase 1/2 · Clarity Pharmaceuticals Ltd
Recruiting sites: California, Louisiana, Michigan, Minnesota, Missouri, Nebraska, New York
Read full eligibility criteria
Inclusion Criteria:
* Signed informed consent;
* ≥18 years of age;
* Eastern Cooperative Oncology Group performance status of 0 to 2;
* Life expectancy \>6 months;
* Histological, pathological, and/or cytological confirmation of Prostate cancer (PCa);
* Positive 64Cu-SAR-bisPSMA PET/CT scan, where 64Cu-SAR-bisPSMA uptake (standardized uptake value \[SUV\] max) of at least 1 known lesion is higher than that of the liver on the 1 hour positron emission tomography (PET)/computed tomography (CT) scan;
* Castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L);
* Have progressive metastatic castration-resistant prostate cancer (mCRPC) despite prior androgen deprivation therapy and:
* Dose Escalation: at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors \[androgen receptor pathway inhibitorsARPIs\]).
* Cohort Expansion Main Group: Participant has progressed once or twice on a prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). No concomitant ARPI on study. Note: First generation ARPI is allowed but not considered as prior ARPI. Second generation ARPI must be the most recent therapy received.
* Cohort Expansion Concomitant Enzalutamide Group: Participant has progressed only once on prior second generation ARPI (prior abiraterone, darolutamide, or apalutamide is allowed, prior treatment with enzalutamide is not allowed). Note: First generation ARPI is allowed but not considered as prior ARPI. Second generation ARPI must be the most recent therapy received.
Documented progressive mCRPC will be based on at least 1 of the following criteria:
1. Serum/plasma prostate specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal value for study enrollment is 2.0 ng/mL;
2. Soft-tissue progression defined as a ≥20% increase in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since the last treatment directed at the metastatic cancer has started (not including hormonal therapy) or the appearance of 1 or more new lesions;
3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan.
* ≥1 metastatic lesion that is present at screening CT, magnetic resonance imaging (MRI), or bone scan imaging obtained ≤28 days prior to enrollment into the study;
* Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (prior chemotherapy, radiation, immunotherapy, etc.);
* Participants must have adequate organ function:
* Bone marrow reserve:
* White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 109/L is equivalent to 2.5 x 103/μL and 2.5 x K/μL and 2.5 x 103/cc and 2500/μL) OR
* Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1.5 x 109 /L is equivalent to 1.5 x 103 /μL and 1.5 x K/μL and 1.5 x 103 /cc and 1500/μL);
* Platelets ≥100 x 109 /L (100 x 109 /L is equivalent to 100 x 103 /μL and 100 x K/μL and 100 x 103 /cc and 100,000/μL);
* Hemoglobin ≥9 g/dL (5.59 mmol/L);
* Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted;
* Alanine aminotransferase or aspartate aminotransferase ≤3.0 x ULN OR ≤5.0 x ULN for participants with liver metastases;
* Creatinine clearance or estimated glomerular filtration rate ≥50 mL/min
* For participants who are human immunodeficiency virus infected: Participant must be healthy and have a low risk of Acquired Immune Deficiency Syndrome related outcomes in the opinion of the Investigator;
* For participants who have partners of childbearing potential: Partner and/or participant must use a method of birth control with adequate barrier protection.
Exclusion Criteria:
* Major surgery within 12 weeks prior to enrollment into the study;
* Brain metastasis;
* Histologic diagnosis of small cell or neuroendocrine prostate cancer;
* Prior history of leukemia or Myelodysplastic Syndrome;
* Diagnosis of Deep Vein Thrombosis or Pulmonary Embolism within 4 weeks prior to enrollment into the study;
* Unmanageable urinary tract obstruction;
* Evidence of progressive lesion(s) on MRI and/or CT (according to Response Evaluation Criteria in Solid Tumors V1.1) that is prostate-specific membrane antigen (PSMA) negative on the 1 hour 64Cu-SAR-bisPSMA PET/CT scan as determined at screening. NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE 64Cu-SAR-bisPSMA DOSIMETRY PHASE AND DOSE ESCALATION PHASE.
* Previous treatment with a systemic radionuclide:
* Dose Escalation: Previous treatment with a systemic radionuclide, including 177Lu, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Actinium-225, Iodine-131 within 6 months or in case of Radium-223 within 3 months of treatment initiation (Day 0) without prior approval of the medical monitor;
* Cohort Expansion: Previous treatment with a systemic radionuclide, including Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Iodine-131 within 6 months or in case of Radium-223 within 3 months of treatment initiation (Day 0) without prior approval of the medical monitor; Any previous PSMA targeted radionuclide therapy (including 177Lu and Actinium-225) is also excluded.
* Previous treatment with any systemic anti-cancer therapy (e.g. immunotherapy or biological therapy \[including monoclonal antibodies\]) within 4 weeks prior to treatment on study with the exception of Luteinizing Hormone Releasing Hormone (LHRH), any other androgen deprivation therapy (ADT) or low dose corticosteroids.
* Dose Escalation: prior treatment with chemotherapy within 4 weeks of first administration of 67Cu-SAR-bisPSMA is also excluded.
* Cohort Expansion: Prior treatment with cytotoxic chemotherapy for castration resistant PCa (e.g. taxanes, platinum, estramustine, vincristine, methotrexate, etc) is also excluded. Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with any poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) is also excluded. NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE 64Cu-SAR-bisPSMA DOSIMETRY PHASE;
* Previous treatment with any investigational agents within 4 weeks prior enrollment into the study;
* Known hypersensitivity to the components of the investigational products or its analogues;
* Transfusion for the sole purpose of making a participant eligible for study inclusion;
* Spinal metastasis with symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression;
* Concurrent serious medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation;
* Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer, superficial bladder cancer;
* Any condition or personal situation that would pose an unacceptable radiation safety risk (as per institution guidelines, state and/or national regulations) to the participant or carer at the time of release following the completion of therapy (e.g. uncontrolled urinary incontinence, high dependency care);
* Participants in whom it is known that external beam radiation therapy is scheduled after enrollment into the study. NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE 64Cu-SAR-bisPSMA DOSIMETRY PHASE.
* Participants in the Cohort Expansion Concomitant Enzalutamide Group:
1. Participants with known hypersensitivity to enzalutamide or any of its ingredients.
2. Participants with a history of seizures.
3. Participants with a history of loss of consciousness (unless of cardiac origin) or transient ischemic attack within 12 months prior to enrolment into the study.
4. Participants with conditions that increase the risk of seizures include those with a history of traumatic brain injury, stroke or cerebrovascular disease, arteriovenous malformations in the brain, neurodegenerative diseases, primary or metastatic brain tumors, active leptomeningeal disease, uncontrolled hypertension (systolic \>179 or diastolic \>105), patients undergoing alcohol withdrawal.
68Ga-PSMA-11 PET-directed Radioligand Therapy in Metastatic Hepatocellular Carcinoma (HCC)
177Lu-PSMA-617, a PSMA-targeted radioligand therapy, is being studied in PSMA-PET-positive metastatic or unresectable hepatocellular carcinoma after progression on prior anti-PD-L1-containing systemic therapy.
NCT06852820 · Phase 2 · Melissa Lumish
Recruiting sites: Ohio
Read full eligibility criteria
Inclusion Criteria:
* Participants must have histologically, cytologically or radiographically confirmed hepatocellular carcinoma by LI-RADS30 with metastatic and/or unresectable disease.
* Participants must have received one prior line of systemic therapy for the treatment of metastatic and/or unresectable HCC including anti-PD-L1 therapy. Participants will be enrolled at the time of progression on first-line therapy for metastatic and/or unresectable disease.
* Age \>18 years. Because no dosing or adverse event data are currently available on the use of 177Lu-PSMA-617 (Lu-177 vipivotide tetraxetan) in participants \<18 years of age, children are excluded from this study.
* ECOG performance status 0 or 1.
* Participants must have normal organ and marrow function as defined below:
Absolute Neutrophil Count ≥ 1,500/mcL. Hemoglobin \> 9 g/dL. Platelet count ≥ 75,000/mcL. Serum creatinine ≤ 1.5 x institutional upper limit of normal or CrCl ≥60 mL/min using the Cockroft-Gault formula for participants with creatinine levels \>1.5 ULN.
Child-Pugh class A or B7.
* At least one target lesion measurable by RECIST 1.1 criteria.
* PSMA-PET demonstrating PSMA PET positive lesion (higher uptake in the tumor compared with background liver uptake).
* Participants must have the ability to understand and the willingness to sign a written informed consent document.
* Participants of childbearing age are using an appropriate method of contraception.
Exclusion Criteria:
* Participants receiving any other investigational agents.
* Subject has received investigational therapy within 4 weeks or within 5 half-lives of the therapeutic agent (whichever is shorter).
* Ongoing grade 3 or higher toxicity from prior anticancer systemic therapy.
* Prior treatment with Y90 radioembolization for hepatocellular carcinoma.
* Participants who have undergone major surgery within 3 months of screening and have not adequately recovered.
* Known additional malignancy that currently requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
* Participants with untreated brain metastases and/or carcinomatous meningitis will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases and are not using steroids for at least 7 days prior to trial treatment.
* Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Participants with known psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the treating investigator.
* Subject is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months for females and 14 weeks for males after the last dose of trial treatment. Pregnant or breastfeeding women are excluded from this study because 177Lu-PSMA-617 has not been previously studied in this population and the potential for teratogenic or abortifacient effects are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to the treatment of the mother with 177Lu-PSMA-617, breastfeeding should be discontinued if the mother is treated with 177Lu-PSMA-617. These potential risks may also apply to 68Ga-PSMA-11 used in this study.
* Subject has received live vaccine within 30 days prior to the first dose of trial treatment.
* Subject with recent variceal bleeding, gastrointestinal bleeding or high risk of bleeding.
9-ING-41 Combined With Retifanlimab, Plus Modified FOLFIRINOX for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)
Phase 1 trial of 9-ING-41 (elraglusib), a GSK-3β inhibitor, combined with the PD-1 inhibitor retifanlimab plus modified FOLFIRINOX chemotherapy in previously untreated advanced/metastatic pancreatic adenocarcinoma.
NCT06896188 · Phase 1 · Anwaar Saeed
Recruiting sites: Pennsylvania
Read full eligibility criteria
Inclusion Criteria:
* Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.
* Is aged ≥ 18 years.
* Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced/metastatic setting.
* Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post radiation on a subsequent scan prior to trial enrollment.
* Must have available archived FFPE tumor tissue at study entry; FFPE tissue block preferred or 10 unstained slides (metastatic tissue preferred to primary tissue) OR if FFPE archived tissue is not available, willing to provide a standard fresh tumor biopsy prior to start of study treatment for molecular profiling of the tumor using standard institutional oncomine panel. If oncomine testing has previously been completed, a repeat biopsy or testing is not required.
* Has laboratory function within specified parameters (may be repeated):
* Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL
* Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN
* Adequate renal function: CrCl \> 60 mL/min measured or calculated by Cockcroft-Gault (C-G) equation (estimated glomerular filtration rate \[eGFR\] can also be used in place of CrCl)
* Serum amylase and lipase ≤ 1.5 x ULN
* Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1 (Appendix A)
* Has received the final dose of any of the following treatments/ procedures within the specified minimum intervals before first dose of study drug:
* Focal radiation therapy - 7 days
* Surgery with general anesthesia - 7 days
* Surgery with local anesthesia - 7 days
* May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment.
* May have received neoadjuvant chemotherapy with FOLFIRINOX if given at least 6 months before study enrollment.
* May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if given at least 6 months before study enrollment.
* Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal AND barrier method of birth control, or true abstinence) for the duration of study participation and in the following 9 months after discontinuation of study treatment.
* Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 9 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence.
* Must not be receiving any other investigational medicinal product.
Exclusion Criteria:
* Is pregnant or lactating.
* Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor.
* History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent.
* Has endocrine or acinar pancreatic carcinoma.
* Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).
* Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening.
* Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the treating investigator or PI.
* Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug.
* Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered). In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major.
* Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation.
* Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.
* Has a current malignancy other than pancreatic cancer.
* Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent).
* Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
* Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.
* Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.
* Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment-related standard premedication are permitted.
* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
* Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is \> 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids for this purpose, and not have had radiation pneumonitis.
* Has received systemic antibiotics ≤ 7 days prior to the first dose of study drug.
* History of organ transplant, including allogeneic stem cell transplantation.
* Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
* Known allergy or hypersensitivity to any component of retifanlimab or formulation components.
* Has received a live vaccine within 28 days of the planned start of study drug.
* Patients with known history of UGT1A1 gene polymorphism.
90Y Transarterial Radioembolization Versus Microwave Ablation in Small Hepatocellular Carcinoma With Hypoalbuminemia
This trial randomizes patients with newly diagnosed small, early-stage hepatocellular carcinoma and hypoalbuminemia to first-line treatment with either 90Y Therasphere transarterial radioembolization or microwave ablation.
NCT05953961 · Phase N/A · Ochsner Health System
Recruiting sites: Louisiana
Read full eligibility criteria
Inclusion Criteria:
* HCC diagnosis according to the Liver Imaging - Reporting Data System (LI-RADS) Criteria as defined in the American Association for the Study of Liver Diseases 2018 HCC practice guidelines
* Eastern Cooperative Oncology Group score 0 - 1
* Child-Pugh A - B
* Bilirubin \< 2.5 mg/dL
* Creatinine \< 2.0 mg/dL
* No prior liver-directed therapy or systemic therapy for HCC
* Solitary, unresectable HCC ≤ 3cm
* Albumin level \< 3.4 g/dL at HCC diagnosis
* Tumor anatomical location and angiosome amendable to MWA and 90Y
Exclusion Criteria:
* Pregnant women
* Concurrent malignancy
A 2-part Phase 1/2 Open-label Trial on ODM-212
ODM-212, an oral pan-TEAD inhibitor, is being studied alone or with standard regimens (ipilimumab/nivolumab, gemcitabine/nab-paclitaxel, or sotorasib) in advanced mesothelioma, metastatic pancreatic adenocarcinoma, and KRAS G12C-mutant advanced/metastatic NSCLC.
NCT07563738 · Phase 1/2 · Orion Corporation, Orion Pharma
Recruiting sites: California, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Male or female participants ≥18 years old.
* Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* Life expectancy of \>12 weeks, in the opinion of the investigator.
* Ability to take oral medications and willing to record daily adherence to investigational product.
* Part 1: Participants with histologically or cytologically confirmed advanced or metastatic, unresectable solid tumors and who are able and willing to receive one of the anti-cancer therapies studied in this trial according to the investigator.
* Arm A: Participants with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma who are eligible to receive treatment with ipilimumab/nivolumab; participants must not have undergone surgical therapy for mesothelioma.
* Arm B: Participants with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas who are eligible to receive treatment with nab-paclitaxel and gemcitabine.
* Arm C: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C-mutation, confirmed using a validated test, who have received the available 1st line treatment and who are eligible for a treatment with sotorasib and have not received a KRAS G12C inhibitor as prior treatment.
Part 2:
* Ipilimumab/nivolumab cohort: Participants with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma who are eligible to receive a treatment with ipilimumab/nivolumab. Prior treatment with ipilimumab, nivolumab and/or other PD-1/PD-L1/CTLA-4 inhibitors for advanced or metastatic disease is not allowed.
* Nab-paclitaxel/gemcitabine cohort: Participants with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas who are eligible to receive a treatment with nab-paclitaxel and gemcitabine. Previous treatments with nab-paclitaxel and/or gemcitabine for metastatic disease are not allowed.
* Sotorasib cohort, treatment naïve: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C-mutation, confirmed using a validated test, who are eligible for a treatment with sotorasib and have not received a KRAS G12C inhibitor as prior treatment.
* Sotorasib cohort, pretreated: Participants with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C mutation, confirmed using a validated test, who have documented progression on a prior KRAS G12C inhibitor (approved or investigational).
* Part 2 only: Participants must have measurable disease by response evaluation criteria in solid tumours (RECIST) v. 1.1 (modified RECIST for MPM).
* A recent (taken up to 1 year ago), representative tumour tissue sample (from primary tumour or from metastasis) must be available. Tissue must be a core needle biopsy, excisional or incisional biopsy. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumour samples are also not acceptable.
* Amenable for paired fresh tumour biopsy at screening period and on-treatment.
Exclusion Criteria:
* Other malignancy active within the previous 2 years except for basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast, for which the participants has completed curative therapy.
* Prior chemotherapy, immunotherapy (immune checkpoint inhibitor, tumour vaccine, cytokine or growth factor given to control the cancer) or other anti-cancer therapy within less than 2 weeks before trial treatment administration.
* Any persistent unresolved toxicity from previous anti-cancer therapies of CTCAE Grade ≥ 2 (except for peripheral neuropathy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities). Ongoing adjuvant treatments for previous cancers are allowed as concomitant treatments if they do not have direct anti-tumour effect on the index tumour (e.g. hormone-suppressing agents).
* Prior definitive radiation therapy within less than 4 weeks and prior palliative radiotherapy within less than 2 weeks before trial treatment administration. Radiopharmaceuticals should be expected to have cleared sufficiently from the participant's body before trial treatment administration.
* Participants with brain or subdural metastases are not eligible, unless the metastases are asymptomatic and have been adequately treated with local therapy.
* Any severe active infection within 1 week of trial enrolment.
* Known positive tests for hepatitis B surface antigen or hepatitis C virus (HCV) RNA; known human immunodeficiency virus (HIV) infection. Screening test is not required unless participant has clinical findings suggestive of HIV, HBV or HCV infection.
* Major surgery within 4 weeks before the first dose of trial treatment or minor surgery within 1 week (participant must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2).
* Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses \>10 mg/day prednisone or equivalent) within 2 days before trial treatment administration.
* Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g. nausea, diarrhoea, or vomiting) that might impair the bioavailability of ODM-212.
* Use of other investigational medicinal products within 2 weeks or at least 5 half-lives (whichever is longer) before trial treatment administration, or any persistent unresolved toxicity from such treatment that, according to the judgement of the investigator, may pose a health risk for the participant, if taking part in the trial. For drugs such as investigational monoclonal antibodies with half-lives \>10 days, at least 8 weeks is required. In addition, all visits (apart from survival follow-up) related to the use of another IMP must be completed before dosing with trial treatments may commence.
* Use of any live or live-attenuated vaccines (e.g., intranasal influenza, measles, mumps, rubella, shingles, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days prior to the first dose of study drug.
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 ms, a prolonged QTc interval (QTcF/B \>470 ms) as demonstrated by 2 out of 3 repeated ECG at screening, performed according to local practice. A history of risk factors for torsade de pointes (e.g. heart failure, hypokalaemia, family history of long QT Syndrome) or the use of drugs that prolong the QT interval and are clearly associated with a known risk of torsade de pointes, even when taken as recommended per Crediblemeds.org QTdrugs list.
* Significant cardiovascular impairment: history of congestive heart failure of New York Heart Association (NYHA) Class III-IV, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke, left ventricular ejection fraction (LVEF) \<50%, cardiac arrhythmia requiring medical treatment (including oral anticoagulation) within 6 months prior to the first dose of trial treatment.
* Female participants who are breastfeeding or pregnant at screening or baseline. A separate baseline assessment for pregnancy is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
A Beta-only IL-2 ImmunoTherapY Study
MDNA11, an engineered long-acting IL-2 superkine targeting the IL-2 receptor beta subunit (CD122), is being studied alone or with pembrolizumab (anti-PD-1) in patients with advanced/metastatic solid tumors across multiple histologies.
NCT05086692 · Phase 1/2 · Medicenna Therapeutics, Inc.
Recruiting sites: California, Florida, Georgia, Michigan, Texas
Read full eligibility criteria
Key Inclusion Criteria:
1. Aged at least 18 years (inclusive at the time of informed consent).
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
3. Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
4. Histologically or cytologically confirmed locally advanced or metastatic solid tumor (see tumor types listed under conditions)
5. Demonstrated adequate organ function
6. Measurable disease as per Response Evaluation Criteria in Solid Tumors, (RECIST v1.1) and documented by CT and/or MRI.
7. Life expectancy of ≥ 12 weeks.
8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and within 72 hours before the first dose of study drug(s). Women must not be breastfeeding.
9. Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control.
Key Exclusion Criteria:
1. Last administration of prior antitumor therapy:
* Prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to start of treatment.
* Prior radiotherapy within 2 weeks prior to start of treatment or has had a history of radiation pneumonitis. A 1-week washout is required for palliative radiation (\<2 weeks of radiotherapy) to non-CNS disease.
* Radiation therapy to the lung that is \> 30Gy within 6 months prior to start of treatment.
* Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to start of treatment. Concomitant participation in an observational study must be discussed on a case-by-case basis with the MM for approval.
2. Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to start of treatment, subject to discussion with MM.
3. Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers.
4. Condition requiring long-term systemic treatment with either corticosteroids \> 10 mg daily prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to start of treatment.
5. Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
6. Severe pulmonary, cardiac or other systemic disease.
7. Known hepatitis B or C virus infection.
8. Females who are pregnant or lactating or planning to become pregnant during the study.
9. Has had an allogeneic tissue/solid organ transplant.
10. Active infection requiring systemic therapy.
11. Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
12. Any other underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug(s) unsafe or obscure the interpretation of toxicity determination or adverse events.
13. Known severe hypersensitivity to any component of study drug(s).
14. Inability to comply with study and follow up procedures as judged by the Investigator.
A Cancer Vaccine (STEMVAC) in Combination With Chemotherapy for the Treatment of PD-L1 Negative Metastatic Triple-Negative Breast Cancer
STEMVAC, a polyepitope plasmid DNA vaccine targeting CD105/Yb-1/SOX2/CDH3/MDM2 given with sargramostim, is studied in combination with standard-of-care chemotherapy for PD-L1 negative metastatic triple-negative breast cancer.
NCT07078604 · Phase 2 · University of Washington
Recruiting sites: Washington
Read full eligibility criteria
Inclusion Criteria:
* Patients must be at least ≥ 18 years of age
* Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients \< 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable
* Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2
* Histologically confirmed triple-negative breast cancer
* Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included
* HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2023 "Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update" which reaffirms the 2018 "HER2 Breast Testing Guideline Focused Update"
* Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay
* Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
* Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions
* Patients can not have received any prior cancer immunotherapy in the metastatic setting
* Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed
* Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement
* Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed
* A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required
* Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary)
* Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions
* Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment
* Willing to undergo up to two serial biopsies while on study
* White blood cell (WBC) ≥ 2.5 THOU/uL (Within 28 days of receiving first study vaccine)
* Lymphocyte count ≥ 0.5 THOU/uL (Within 28 days of receiving first study vaccine)
* Absolute neutrophil count (ANC) ≥ 1.0 THOU/uL (Within 28 days of receiving first study vaccine)
* Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine)
* Platelets ≥ 75 THOU/uL (Within 28 days of receiving first study vaccine)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \< 3.0 mg/d (Within 28 days of receiving first study vaccine)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine)
* Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance \> 60 mL/min (Within 28 days of receiving first study vaccine)
* Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study until the end of treatment on study
Exclusion Criteria:
* Patient has received more than one line of prior therapy in metastatic setting
* Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay
* Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed. Participation in a trial for chimeric antigen receptor (CAR)-T cell therapy may be permitted if the CAR-T cell therapy is not planned to occur until after the currently proposed treatment (i.e. no longer participating in STEMVAC and chemotherapy trial)
* Patients with any of the following cardiac conditions:
* Symptomatic restrictive cardiomyopathy
* Dilated cardiomyopathy
* Unstable angina within 4 months prior to enrollment
* New York Heart Association functional class III-IV heart failure on active treatment
* Symptomatic pericardial effusion
* Patients with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted
* Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
* A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance
* Pregnant and breastfeeding individuals
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive), or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
* Major surgery within the 4 weeks prior to initiation of study vaccine
* Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination
* Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine
* Any condition that may interfere with the patient's participation in the study per treating physician
A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)
This phase 3 trial compares oral belzutifan (a HIF-2α inhibitor) plus zanzalintinib versus cabozantinib in patients with recurrent, unresectable advanced clear cell renal cell carcinoma that has relapsed during or shortly after adjuvant anti-PD-1/L1 therapy.
NCT07227402 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Alaska, California, Maine, Maryland, Minnesota, Nebraska, North Carolina, Tennessee
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Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition)
* Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
* Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy
* Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
* Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
* Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
* Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications
* Has current pneumonitis/interstitial lung disease
* Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization
* Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation
* Has a serious active nonhealing wound/ulcer/bone fracture
* Has a requirement for hemodialysis or peritoneal dialysis
* Has history of human immunodeficiency virus infection
* Has hepatitis B or hepatitis C virus
* Has pharmacologically uncompensated, symptomatic hypothyroidism
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Calderasib, an oral KRAS G12C inhibitor, is being studied in combination with cetuximab (anti-EGFR antibody) and mFOLFOX6 chemotherapy versus mFOLFOX6 with or without bevacizumab as first-line treatment for locally advanced unresectable or metastatic KRAS G12C-mutant colorectal adenocarcinoma.
NCT06997497 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Arizona, California, Colorado, Florida, Georgia, Idaho, Illinois, Iowa, Kentucky, Maryland, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Jersey, New Mexico, New York, North Carolina, Ohio, Pennsylvania, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
* Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
* Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
* Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)
Calderasib, an oral KRAS G12C inhibitor, combined with subcutaneous pembrolizumab/berahyaluronidase alfa is being studied versus pembrolizumab plus chemotherapy as first-line treatment for advanced/metastatic nonsquamous NSCLC.
NCT07190248 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Alabama, Connecticut, Florida, Georgia, Indiana, Maine, New Jersey, New York, Oregon, Pennsylvania, Virginia
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has nonsquamous NSCLC (Stage IIIB, Stage IIIC) not eligible for curative resection or chemoradiation or Stage IV: M1a, M1b, or M1c
* If human immunodeficiency virus (HIV) positive, must have well controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has a gastrointestinal disorder affecting absorption
* Is HIV positive and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy for their advanced or metastatic NSCLC
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy except those specified by protocol
* Has history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications
A Clinical Study of Calderasib (MK-1084) in People With Advanced Solid Tumors (MK-1084-014)
Calderasib (MK-1084), an oral KRAS G12C-targeted agent, is studied alone or in combination with the EGFR-targeted antibody cetuximab in patients with advanced/metastatic KRAS G12C-mutant solid tumors (excluding colorectal cancer) who progressed on prior standard therapy.
NCT07209111 · Phase 2 · Merck Sharp & Dohme LLC
Recruiting sites: Maryland, Michigan, Nevada, New Jersey, Utah, Virginia
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has locally advanced unresectable or metastatic solid tumor malignancy other than colorectal cancer and has progressed on, or following, standard of care systemic treatment
* Has a tumor that demonstrates the presence of Kirsten rat sarcoma (KRAS) G12C mutation
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system metastases and/or carcinomatous meningitis and/or primary brain tumors
* Has active infection, other than those permitted per protocol, requiring systemic therapy
* Has not adequately recovered from major surgery or has ongoing surgical complications
A Clinical Study of Gocatamig (MK-6070) and Infinatamab Deruxtecan (MK-2400) in People With Small Cell Lung Cancer (MK-6070-003)
This trial studies gocatamig (a T-cell engager) combined with ifinatamab deruxtecan (I-DXd, an antibody-drug conjugate), alone or with standard platinum/etoposide chemotherapy and/or atezolizumab immunotherapy, as induction and/or maintenance treatment for first-line extensive-stage small cell lung cancer.
NCT07227597 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: California, Colorado, Florida, Kentucky, Missouri, New Jersey, Oregon, South Dakota, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC)
* For participants receiving gocatamig + ifinatamab deruxtecan (I-DXd) in maintenance only:
* Completed 3 to 4 cycles of platinum + etoposide chemotherapy with concurrent approved anti-programmed cell death 1/Ligand 1 (anti PD-1/L1) as first line (1L) treatment of ES-SCLC within 6 weeks prior to enrollment
* No radiological disease progression per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
* No other prior systemic ES-SCLC therapy allowed
* Rechallenge therapy counts as an additional line and leads to exclusion
* For participants receiving gocatamig + I-DXd in induction and maintenance, or gocatamig + I-DXd in induction followed by gocatamig + atezolizumab in maintenance, or carboplatin + etoposide + atezolizumab in induction followed by atezolizumab in maintenance: No prior systemic ES-SCLC treatment allowed
* Applicable to all participants: prior limited-stage small cell lung cancer (SCLC) is allowed if \> 6 months have passed since the end of previous therapy and progression
* Must be able to provide a pretreatment archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated
* Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if growth has been shown in such lesions since the completion of radiation
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, current ILD, ILD that cannot be ruled out by imaging at screening, or suspected ILD
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Has history of clinically significant intracranial bleeding or spinal cord bleeding
* Has active neurologic paraneoplastic syndrome
* Has history of coronary/peripheral artery bypass graft and/or any coronary/peripheral angioplasty or clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (CHF), and/or uncontrolled cardiac arrhythmia within 6 months before the first dose of study intervention
* Has other uncontrolled or significant protocol specified cardiovascular disease
* Has history of arterial thrombosis within 6 months before the first dose of study intervention
* Has chronic liver disease
* Has history of allogeneic tissue/solid organ transplant
* Has history of leptomeningeal disease
* Is infected with human immunodeficiency virus (HIV) and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has major surgery within 4 weeks or minor surgery within 2 weeks of allocation/randomization (or first dose), or is anticipated to require a major surgical procedure during the study
A Clinical Study of Ifinatamab Deruxtecan (I-DXd) in People With Metastatic Prostate Cancer (MK-2400-001)
Ifinatamab deruxtecan, a B7-H3-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor payload, is being compared to docetaxel chemotherapy in metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitors.
NCT06925737 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Arizona, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Illinois, Kentucky, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nebraska, Nevada, New Jersey, New Mexico, New York, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Virginia, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months prior to Screening
* Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography (CT)/magnetic resonance imaging (MRI)
* Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after at least 8 weeks of treatment
* Has provided tumor tissue from a core or excisional biopsy from soft tissue not previously irradiated and obtained after disease progression on the most recent prior therapy
* Has recovered from adverse events (AEs) due to previous anticancer therapies
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Is unable to swallow tablets/capsules
* Has any of the following indicators of interstitial lung disease (ILD)/pneumonitis:
1. Has any history of ILD/pneumonitis that required steroid use, except for a history of radiation pneumonitis that did not require steroids
2. Has current ILD/pneumonitis
3. Has a clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Has uncontrolled or significant cardiovascular disease
* Has received prior treatment with a taxane-based chemotherapy agent for metastatic castration-resistant prostate cancer (mCRPC)
* Has had prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities
* Has a "superscan" bone scan
A Clinical Study of Ifinatamab Deruxtecan Based Treatment Combinations or as Monotherapy to Treat Metastatic Castrate Resistant Prostate Cancer (mCRPC) (MK-2400-01A/IDeate-Prostate02)
Ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate delivering a topoisomerase I inhibitor payload, is being studied alone or combined with agents such as opevesostat, abiraterone, enzalutamide, or docetaxel in metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitors.
NCT06863272 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: California, District of Columbia, Michigan, New York, Pennsylvania, Tennessee, Washington
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before Screening
* Has current evidence of distant metastatic disease
* Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after treatment
* Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks before allocation/randomization
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 10 days before allocation/randomization
* Has prior treatment with poly-ADP-ribose polymerase inhibitors (PARPi) if indicated by local approved regimen or were deemed ineligible to receive PARPi by the investigator
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), current ILD, clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Uncontrolled or significant cardiovascular disease
* History of pituitary dysfunction
* Poorly controlled diabetes mellitus
* History or current condition of adrenal insufficiency (eg, Addison's disease)
* Has received prior treatment with taxane-based chemotherapy agent for metastatic castration-resistant prostate cancer (mCRPC).
* Chronic steroid treatment (dose of \>10 mg daily prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease), topical steroids (for mild skin conditions), or intra-articular steroid injections
* Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic treatment in the past 2 years
* History of allogeneic tissue/solid organ transplant
A Clinical Study of Intismeran Autogene (V940) and BCG in People With Bladder Cancer (V940-011/INTerpath-011)
Intismeran autogene (V940), an individualized mRNA neoantigen cancer vaccine, is being studied in combination with BCG versus BCG alone in patients with high-risk non-muscle invasive bladder cancer following TURBT.
NCT06833073 · Phase 2 · Merck Sharp & Dohme LLC
Recruiting sites: California, Colorado, Florida, Illinois, Louisiana, Missouri, Nebraska, New York, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
\- Is an individual whose most recent TURBT was performed within 12 weeks before randomization/allocation and showed BICR-confirmed high-risk NMIBC histology
Cohort A:
* Has high-risk non-muscle invasive (HG Ta, T1, and/or CIS) UC of the bladder
* Is BCG-naïve defined as either having never received BCG or having received BCG more than 2 years before high-risk NMIBC recurrence. Recurrence must be at least 24 months from the last exposure to BCG with evidence of complete response during the 2-year period post BCG
Cohort B:
* Has CIS +/-papillary non-muscle invasive UC of the bladder
* Is ineligible for, or refusing, any IVESIC therapy
* Is either BCG-naïve (as defined above) or BCG-exposed but did not receive protocol-specified minimum dosing of BCG and experienced recurrence of high-risk NMIBC within 2 years of the last dose of BCG
* Human immunodeficiency virus (HIV)-infected individuals must have well controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has a history of or concurrent locally-advanced (ie, T2, T3, T4) or metastatic UC
* Has concurrent extravesical (ie, urethra, ureter, renal pelvis) non-muscle invasive UC or a history of extravesical non-muscle invasive UC that recurred within the last 2 years, with certain exceptions
* Has a known additional malignancy that is progressing or has required active treatment within the last 3 years
* Has had a myocardial infarction within 6 months of randomization/allocation
* Has received any systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation
* Has received prior treatment with a cancer vaccine
* Has immunodeficiency or is receiving chronic systemic steroid therapy
* Has active autoimmune disease that has required systemic treatment in the last 2 years
* Has any contraindication to IV contrast and gadolinium or is otherwise unable to have imaging with either computerized tomography urogram (CTU) or Magnetic resonance urography (MRU)
Cohort A:
* Has current active tuberculosis
* Has a known history of HIV infection
Cohort B:
\- HIV-infected individuals with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
A Clinical Study of Intismeran Autogene (V940) and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012)
Intismeran autogene, an individualized mRNA neoantigen cancer vaccine, is studied in combination with pembrolizumab versus placebo plus pembrolizumab in patients with unresectable Stage III/IV cutaneous melanoma who are untreated for advanced disease.
NCT06961006 · Phase 2 · Merck Sharp & Dohme LLC
Recruiting sites: Arkansas, California, New Jersey, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has unresectable and histologically confirmed Stage III or IV cutaneous melanoma per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
* Has been untreated for melanoma except if participant received prior adjuvant or neoadjuvant therapy with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein \[CTLA-4\], anti-programmed cell death 1 protein \[PD-1\] therapy or interferon), and only if relapse did not occur within 12 months after treatment discontinuation.
* Have documentation of serine/threonine-protein kinase B-raf (BRAF) V600-activating mutation status or had BRAF V600 mutation testing per local institutional standards during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild-type or unknown are eligible).
* Have the presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment.
* Provides tumor tissue (preferably from a metastatic site and, if not available, from the primary tumor) that is suitable for next generation sequencing and biomarker analysis as required for this study.
* Participants with human immunodeficiency virus (HIV) must have well controlled HIV on antiretroviral therapy (ART).
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has clinically significant heart failure, defined as New York Heart Association class III or IV, within the past 6 months, unless the disease is well controlled in the opinion of the investigator.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has ocular or mucosal melanoma.
* Received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the Screening blood sample (including the blood sample for V940 generation).
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, lymphocyte activation gene 3 \[LAG-3\], tumor necrosis factor receptors \[OX-40 or CD137\]), with some exceptions.
* Received prior systemic anticancer therapy for melanoma before randomization, with some exceptions.
* Received prior radiotherapy within 2 weeks of start of study intervention or has ongoing radiation related toxicities.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Received prior treatment with another universal or personalized cancer vaccine.
A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
T3011, an intratumorally injected oncolytic HSV-1 engineered to express IL-12 and an anti-PD-1 antibody, is being studied alone and with intravenous pembrolizumab in patients with advanced/metastatic melanoma, HNSCC, sarcoma, cutaneous squamous cell carcinoma, and NSCLC who have progressed on standard therapy.
NCT04370587 · Phase 1/2 · ImmVira Pharma Co. Ltd
Recruiting sites: Arizona, Massachusetts, Pennsylvania, Texas, Virginia
Read full eligibility criteria
Key Inclusion Criteria:
1. Age 18 years or older.
2. Disease progression after standard of care (SOC) therapy or in the opinion of
3. The Investigator unlikely to benefit from SOC therapy. Inclusion Diagnosis Phase 1 - Histologically or pathologically confirmed locally recurrent or metastatic advanced malignancy.
Phase 2a Part 1 i. Arm A - locally recurrent or metastatic melanoma. Participants must have received no more than 3 prior regimens for advanced or metastatic disease.
ii. Arm B - locally recurrent or metastatic HNSCC. It must also meet the following criteria: 1) Disease progression to platinum-containing chemotherapy; 2) Failure to anti-PD-1/PDL1 blockade after receiving at least 2 doses alone or in combination.
iii. Arm C - Sarcoma. Participants must have received no more than three lines of prior anti-cancer therapies.
iv. Arm D - locally recurrent or metastatic cSCC. Participants must have received no more than 3 prior regimens for advanced or metastatic disease.
Phase 2a Part 2 i.v. Arm E - Histologically or pathologically confirmed NSCLC that is advanced or recurrent, without EGFR mutation or ALK rearrangement. Participants must have received at least one line but no more than three lines of prior anti-cancer therapies.
4. Measurable disease per RECIST version 1.1.
5. Must have at least 1 tumor lesion that is accessible for IT injection of T3011 in the opinion of the investigator.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
7. Life expectancy \> 12 weeks.
8. Demonstrate adequate organ function as defined by acceptable laboratory testing results.
9. Women of child-bearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, while on study treatment, and for six months after receiving last dose of T3011. WCBP must have a negative serum pregnancy test prior to W1D1.
10. Last dose of previous anticancer therapy ≥ 21 days, radiotherapy \> 21 days, or surgical intervention \> 21 days prior to the first dose of T3011.
11. Recovered from all prior anticancer therapy toxicities.
12. Willingness to provide fresh tumor biopsy specimens as specified in the Schedule of Assessments.
13. Capable of understanding and complying with protocol requirements.
14. Signed and dated institutional review board/independent ethics committee-approved informed consent form before any protocol-directed screening procedures are performed.
Key Exclusion Criteria:
1. Have only uninjectable tumors..
2. Patients with injectable tumors impinging upon major airways or blood vessels.
3. HNSCC only: Prior re-irradiation field containing carotid artery.
4. Greater than 3 distant metastatic lymph node regions and/or metastatic lesions or the largest distant metastases with a diameter of more than 3 cm (non-sarcoma)/5 cm (sarcoma) unless the lesion is to be injected.
5. Prior treatment with another OV (including T-VEC), tumor vaccines, cellular therapy or gene therapy.
6. Prior intolerance to anti-PD-(L)1 monoclonal antibody or history of immunotherapy related non-infectious pneumonitis/interstitial lung disease.
7. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.
8. Requires continued concurrent therapy with any drug active against HSV.
9. Live vaccines, attenuated vaccines within 4 weeks prior to initiation of study treatment (participants vaccinated with inactivated vaccines can be enrolled.
10. Primary or acquired immunodeficient states.
11. Pregnant or lactating.
12. Prior organ transplantation.
13. Active hepatitis B virus, hepatitis C virus, and HIV infection or a positive serological test at Screening within 14 days of dosing with T3011.
14. Active autoimmune disease or medical conditions requiring chronic steroid or immunosuppressive therapy within 4 weeks prior to first administration of study treatment.
15. History of or current central nervous system metastases.
16. History of seizure disorders within 6 months of Screening.
17. Active oral or skin herpes lesion at Screening.
18. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
19. Congestive heart failure, active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina, or clinically significant cardiac arrhythmias.
20. History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody.
18\. Active infection with SARS-CoV-2 virus. 21. Participants with moderate to large amount of pleural effusion, ascites or pericardial effusion who need drug or medical intervention.
22\. Other systemic conditions or organ abnormalities that, in the opinion of the investigator, may interfere with the conduct and/or interpretation of the current study.
A Clinical Study of KTX-2001 in Subjects With Metastatic Castration-Resistant Prostate Cancer (STRIKE-001)
KTX-2001 is a novel agent (mechanism not stated in the registry) given as monotherapy or combined with the AR pathway inhibitor darolutamide in a phase 1 dose-escalation study for men with metastatic castration-resistant prostate cancer who progressed on prior ARPI therapy.
NCT07103018 · Phase 1 · K36 Therapeutics, Inc.
Recruiting sites: California, Florida, Minnesota, New York, North Carolina, Ohio, South Carolina, Texas, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥18 years.
2. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
3. Male participants with mCRPC as defined by PCWG3 criteria.
4. Metastatic disease documented using bone scan for bone metastases (PCWG3 criteria) or by computed tomography (CT) or magnetic resonance imaging (MRI) for soft-tissue metastases. Evidence of metastasis on prostate-specific membrane antigen positron emission tomography alone will not be sufficient for confirmation of metastatic disease.
5. Willingness to undergo a baseline and on-treatment biopsy of a metastatic site if safe and feasible. If tissue from a biopsy of a metastatic site (including bone) obtained within the previous 6 months (prior to treatment start) is available, this tissue may be used, and the baseline biopsy may be omitted.
6. Participants should have progressed on or after receiving an ARPI (eg, abiraterone, enzalutamide, darolutamide, or apalutamide).
7. Adequate renal function (creatinine clearance \>50 mL/min by serum creatinine).
8. Adequate hepatic function (total bilirubin ≤1.5× ULN, total bilirubin \<3× ULN for participants with documented Gilbert's syndrome, AST and ALT ≤2.5× ULN). In case of liver metastases, AST and ALT \<5× ULN is allowed.
9. Adequate hematological function (neutrophils \>1 × 109/L, platelet count \>100 × 109/L, hemoglobin \>9 g/dL) with no prior transfusions within 2 weeks.
Exclusion Criteria:
1. Presence of symptomatic or uncontrolled brain metastases unless adequately treated, not requiring steroids and stable for the last 28 calendar days before signing the ICF. Participants with leptomeningeal disease are excluded without exception.
2. Symptomatic or impending cord compression that has not been treated or stabilized.
3. Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction (such as coagulopathy or encephalopathy), or other reasons which, in the investigator's opinion, could compromise the participant's safety or interfere with or compromise the integrity of the study outcomes.
4. Presence of a drug-related toxicity from prior cancer therapy that has not resolved to Grade ≤1 (with the exception of alopecia and Grade 2 neuropathy) according to NCI-CTCAE Version 5.0.
5. Active, uncontrolled, bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness. In equivocal cases, participants with a negative viral load may be eligible. Eligibility criteria for HIV-positive participants currently on highly active antiretroviral therapy should be evaluated and discussed with the medical monitor and will be based on current and past CD4 and T cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment. Participants with previously treated HBV and HCV with negative viral load are eligible.
6. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect participation in this study.
1. QT interval corrected by Fridericia's formula \>470 msec at screening.
2. Unstable cardiovascular function defined as:
3. Symptomatic ischemia, or
4. Uncontrolled clinically significant conduction abnormalities (ie, ventricular tachycardia on antiarrhythmic agents are excluded; first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block are not excluded), or
5. Congestive heart failure New York Heart Association Class ≥3, or
6. Myocardial infarction within 3 months of the screening visit.
7. Hypertension that cannot be controlled (persistent \>150/90 mmHg despite optimal medical therapy).
7. Current use or anticipated need for food or drugs that are known strong CYP3A inducers or inhibitors, including their administration within 10 days or 5 half-lives of the CYP3A inhibitor, whichever is longer prior to first dose of study drug.
8. Treatment with anticancer therapies including radiotherapy or AR-targeted therapy/androgen biosynthesis inhibitor) within 2 weeks prior to initial study drug dose or within 4 weeks for systemic chemotherapy, radioligand therapy, or other systemic anticancer therapies.
9. Treatment with another investigational agent in the 4 weeks prior to the initial dose of study drug.
10. Major surgical procedures ≤28 days prior to the initial dose of study drug. Participants must have recovered from any of the effects of any major surgery. No waiting period is required following central venous access placement, biopsy collection, or minor surgeries as long as the investigator assesses the impact on study participation.
11. Initiation of hormonal agents with antitumor activity against prostate cancer including 5alpha reductase inhibitors, androgens (eg, testosterone), cytoproterone acetate, etc during study participation (from the time of consent to off-study); however, stable use of 5-alpha reductase inhibitors is permitted, if continuous use for ≥6 months.
12. Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (eg, saw palmetto, PC-SPES, PC-HOPE, St. John's wort, selenium supplements, grape seed extract, etc) within 4 weeks of study drug initiation or plans to initiate treatment with these products/alternative therapies at any point during the study.
For Part B only (KTX-2001 + darolutamide): Current use or anticipated need for drugs that are known as combined P-glycoprotein (P-gp) and strong or moderate CYP3A4 inducers including their administration within 10 days or 5 half-lives of the combined Pgp/CYP3A4 inducer, whichever is longer prior to first dose of darolutamide.
A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)
MK-1084, an oral KRAS G12C inhibitor, is being studied in combination with other agents (patritumab deruxtecan [HER3-targeted ADC], sacituzumab tirumotecan [TROP2-targeted ADC], and cetuximab [anti-EGFR antibody]) for treatment of advanced or metastatic KRAS G12C-mutant non-squamous NSCLC after prior PD-1/PD-L1 and platinum-based therapy.
NCT07286149 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: Florida, Illinois, Oregon
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has histologically or cytologically confirmed diagnosis of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
* Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene (KRAS) mutation of glycine to cysteine at codon 12 (G12C) mutations
* Has documented disease progression after receiving 1-2 prior lines of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy and platinum-based chemotherapy
* Has provided tumor tissue for biomarker analysis from an archival sample or a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Participants with human immunodeficiency virus (HIV) infection must have well-controlled HIV on antiretroviral therapy (ART) per protocol
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has evidence of any leptomeningeal disease
* Has uncontrolled or significant cardiovascular disorder or cerebrovascular disease prior to allocation/randomization
* Has one or more of the following ophthalmological conditions: a) Clinically significant corneal disease b) history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use or current ILD, or suspected ILD
* Has an active infection requiring systemic therapy
* Has not adequately recovered from major surgery or has ongoing surgical complications
A Clinical Study of MK-2870 Alone or With Other Treatments to Treat Gastrointestinal Cancers (MK-9999-02A)
Sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate, is being studied alone or combined with fluorouracil/leucovorin, cisplatin, or pembrolizumab in previously treated advanced/metastatic colorectal cancer, pancreatic ductal adenocarcinoma, and advanced/unresectable biliary tract cancer (including treatment-naive BTC).
NCT06428409 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: California, Colorado, District of Columbia, Florida, Georgia, New York, Texas, Virginia, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has one of the following cancers:
* Unresectable or metastatic colorectal cancer and has received prior therapy for the cancer
* Advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) and has received prior therapy for the cancer
* Advanced and/or unresectable biliary tract cancer (BTC) and has received prior therapy for the cancer
* Advanced and/or unresectable BTC and has not received prior therapy for the cancer
* For participants who have received prior therapy for cancer: Has recovered from any side effects due to previous cancer treatment
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* History of severe eye disease
* For participants who have received prior therapy for cancer: Received prior systemic anticancer therapy including investigational agents within 4 weeks before starting study intervention
* History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening
A Clinical Study of MK-3120 in People With Bladder Cancer (MK-3120-003)
MK-3120, an anti-nectin-4 antibody-drug conjugate delivering a topoisomerase I inhibitor payload, is being studied via intravesical administration after TURBT in patients with high-risk non-muscle invasive bladder cancer.
NCT07222488 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: California, New Jersey, South Carolina, Texas
Read full eligibility criteria
Inclusion Criteria:
* Has histologically confirmed carcinoma in situ (CIS) +/- papillary high-risk non-muscle invasive bladder cancer (NMIBC), confirmed locally.
* Is an individual whose most recent transurethral resection of bladder tumor (TURBT) was performed within 12 weeks before allocation and showed high-risk NMIBC histology. For individuals with papillary tumors (Ta and T1), a complete TURBT must have been performed, as characterized by attainment of a visually complete resection of all papillary tumors (Ta and T1).
* Is either: a) Bacillus Calmette-Guérin (BCG)-naïve, defined as either having never received BCG or having received BCG more than 2 years before CIS +/- papillary high-risk NMIBC recurrence. Recurrence must be at least 24 months from the last exposure to BCG with evidence of complete response during the 2-year period post-BCG OR; b) BCG-exposed and received adequate BCG therapy and had recurrence of CIS +/- papillary high-risk NMIBC \>12 months but ≤24 months after the last BCG dose.
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy.
* Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
Exclusion Criteria:
* Has history of or current locally advanced (ie, T2, T3, T4) or metastatic urothelial cancer (UC).
* Has concurrent extravesical (ie, urethra, ureter, renal pelvis) non-muscle invasive UC or history of extravesical non-muscle invasive UC that recurred within the last 2 years.
* Has active total bladder incontinence, active urinary tract infection, neurogenic bladder, or urethral stricture.
* Has a condition that would prohibit normal voiding (or holding bladder voiding for 1 to 2 hours).
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system metastases and/or carcinomatous meningitis.
* Has active infection requiring systemic therapy.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, or has current pneumonitis/ILD.
* Has not adequately recovered from major surgery or has ongoing surgical complications.
A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)
Patritumab deruxtecan, a HER3-targeted antibody-drug conjugate, is studied versus chemotherapy or trastuzumab deruxtecan in HR+/HER2- unresectable locally advanced or metastatic breast cancer after progression on CDK4/6 inhibitor plus endocrine therapy.
NCT07060807 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Alabama, Arizona, California, Colorado, Delaware, Florida, Kentucky, Nevada, New Jersey, New Mexico, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Texas, Virginia, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a diagnosis of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent
* Has centrally-confirmed HR+ and HER2- results and human epidermal growth factor receptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastatic site or a locally advanced lesion on or after the time of diagnosis of locally advanced unresectable or metastatic breast cancer. A new biopsy obtained after progression of the most recent line of therapy is preferred
* Must have had progression or recurrence on prior cyclin-dependent kinase (CDK)4/6 inhibitor + endocrine therapy (ET) with one of the following:
* Radiographic disease progression, as assessed by the investigator, on CDK4/6 inhibitor + ET as 1L for treatment of unresectable locally advanced or metastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only line of therapy received in the advanced setting, or
* Disease recurrence, either radiographic and/or confirmed histologically via biopsy as assessed by the investigator, while on adjuvant ET in combination with a CDK4/6 inhibitor OR within 24 months from the date of last dose of adjuvant CDK4/6 inhibitor
* Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1 assessed within 7 days before randomization
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has breast cancer amenable to treatment with curative intent
* Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator
* Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) where poly (ADP-ribose) polymerase (PARP) inhibitor(s) is a potential treatment option
* Has current visceral crisis or is at risk for impending visceral crisis that has or may cause imminent organ compromise and/or other life-threatening complications
* Has any of the following: a pulse oximeter reading \<92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has ≥Grade 2 peripheral neuropathy.
* Has clinically significant corneal disease
* Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
* Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate that consists of a topoisomerase I inhibitor (eg, T-DXd) or any other topoisomerase I inhibitor therapy
* Has received prior systemic anticancer therapy within 4 weeks (or 5 half-lives, whichever is shorter) before randomization; participants previously treated with ET plus a CDK4/6 inhibitor may participate as long as at least 2 weeks have elapsed since the last dose of therapy was administered
* Has received prior radiotherapy for non-central nervous system disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has history of (noninfectious) interstitial lung disease (ILD) or pneumonitis irrespective of steroid use, or has current ILD or suspected ILD, or ILD that cannot be ruled out by imaging at Screening
* Has severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
* Has severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients
A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003).
Raludotatug deruxtecan, a CDH6-targeted antibody-drug conjugate, is being evaluated alone or combined with other agents (such as carboplatin/paclitaxel, bevacizumab, pembrolizumab, or MK-2010) in recurrent or newly diagnosed high-grade serous/endometrioid ovarian, fallopian tube, or primary peritoneal cancer across multiple platinum-sensitive and platinum-resistant cohorts.
NCT06843447 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: Connecticut, Kentucky, Louisiana, Massachusetts, New York, Oklahoma, Texas, Utah, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Has pathologically documented diagnosis of high-grade serous or high-grade endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
* Participants in Part 1 cohorts and Part 2 Cohort A-2 Arms 1, 2, and 3, Cohort B-2, and Cohort C-2 Arm 3: Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1
* Participants in Cohort A-1 Arms 2 and 3: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease)
* Participants in Cohort B-1 and Cohort B-2: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression \<6 months (\<180 days) after the last dose of platinum-based therapy (ie, platinum-resistant disease). Participants must have received no more than 1 prior bevacizumab-containing systemic treatment regimen
* Participants in Cohort B-1, Cohort B-2, Cohort C-2 Arm 3, Cohort E-1 and if administering bevacizumab is planned in Cohort D or Cohort A-2 Arms 1, 2, or 3: Is a candidate for bevacizumab treatment
* Has provided tumor tissue for biomarker research (all cohorts)
* Has an Eastern Cooperative Oncology Group performance status of 0 to 1
* Participants in Cohort C-1, Cohort C-2 Arm 3, Cohort D, and Cohort E-1: Has relapsed disease after 1 prior line of therapy, radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) and progressed during prior treatment with poly-ADP ribose polymerase inhibitor (PARPi) in the first-line setting
* Participants in Cohort A-2 Arms 1, 2, and 3: Has relapsed disease after 1 prior line of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease)
* Participants in Cohort C-2 Arms 1 and 2: Has a new, histologically confirmed diagnosis of International Federation of Gynecology and Obstetrics Stage III or Stage IV epithelial ovarian cancer (high-grade serous or high-grade endometrioid), fallopian tube cancer, or primary peritoneal cancer that is non-homologous recombination deficiency-positive
* Participants in Cohort C-2 Arms 1 and 2: According to the investigator's assessment, PARPi first-line maintenance treatment for non- homologous recombination deficiency (HRD)-positive disease is not the preferred option for the participant
* Participants in Cohort C-2 Arms 1 and 2: According to the investigator's assessment, bevacizumab treatment for non-HRD-positive disease is not the preferred option for the participant
Exclusion Criteria:
* Has any of the following within 6 months before allocation/randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
* Has uncontrolled or significant cardiovascular disease
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement, or prior pneumonectomy
* Has ≥Grade 2 peripheral neuropathy
* Has received prior treatment with cadherin-6-targeted agents
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before allocation
* Has received prior radiotherapy within 2 weeks of the start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Receives chronic steroid treatment
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active CNS metastases and/or carcinomatous meningitis
* Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of prior steroid use, current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening
* Has active infection requiring systemic therapy
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate, is studied in combination with pembrolizumab (with or without bevacizumab/chemotherapy) as first-line maintenance treatment for persistent, recurrent, or metastatic cervical cancer.
NCT07216703 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Alabama, Alaska, California, Florida, Georgia, Louisiana, Maryland, Minnesota, Nevada, New York, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, Tennessee, Texas, Virginia
Read full eligibility criteria
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of cervix
* Has persistent, recurrent, or newly diagnosed metastatic (International Federation of Gynecology and Obstetrics \[FIGO\]-2028 Stage IVB) cervical cancer that is not amenable to curative treatment (surgery and/or radiation)
* If infected with human immunodeficiency virus (HIV), has well controlled HIV on antiretroviral therapy
* If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy and has undetectable HBV viral load
* If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1
* Has tumor programmed cell death ligand 1 expression of combined positive score ≥1
The main exclusion criteria include but are not limited to the following:
* Has HIV infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has received prior systemic anticancer therapy other than what is specified in this protocol
* Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 that cannot be discontinued for the duration of treatment with sac-TMT
* Has a diagnosis of immunodeficiency
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system metastases and/or carcinomatous meningitis
* Has active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Patients With Bladder Cancer (MK-2870-027)
Sacituzumab tirumotecan (MK-2870), an antibody-drug conjugate, is being studied via intravesical administration in patients with recurrent intermediate-risk low-grade (Ta) non-muscle invasive bladder cancer to determine tolerability and optimal dose.
NCT06637423 · Phase 1/2 · Merck Sharp & Dohme LLC
Recruiting sites: California, Florida, Illinois, Maryland
Read full eligibility criteria
Inclusion Criteria:
The key inclusion criteria include but are not limited to the following:
* Has recurrent low-grade (Ta) Non-Muscle Invasive Bladder Cancer (NMIBC) in the bladder
* Must have visible tumor by cystoscopy within 12 weeks prior to first dose
* Has intermediate-risk NMIBC defined as 1 or more of the following risk factors:
* Multiple tumors
* \>1 occurrence of low-grade NMIBC within 1 year of the current diagnosis at Screening
* Early recurrence (\<1 year) of the initial diagnosis of low-grade disease
* Solitary tumor \>3 cm
* Failure of prior intravesical treatment
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 14 days prior to first dose
Exclusion Criteria:
The key exclusion criteria include but are not limited to the following:
* Newly diagnosed low-grade non-muscle invasive bladder cancer (Ta NMIBC) in the bladder
* Past or current history of high-grade (Ta or T1 or CIS) NMIBC, muscle invasive bladder cancer (MIBC) or metastatic urothelial carcinoma (UC)
* Has a condition that would prohibit normal voiding (or hold bladder voiding for 1 to 2 hours)
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease, and/or blepharitis, or severe corneal disease that prevents and/or delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Chron's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)
Sacituzumab tirumotecan (a TROP2-directed antibody-drug conjugate) combined with pembrolizumab and chemotherapy, versus pembrolizumab plus chemotherapy, is being studied as neoadjuvant treatment for previously untreated high-risk, early-stage triple-negative or HR-low-positive/HER2-negative breast cancer.
NCT06966700 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Arizona, California, Colorado, Florida, Georgia, Illinois, Indiana, Louisiana, Maine, Maryland, Massachusetts, Missouri, Nebraska, Nevada, New Jersey, North Dakota, Ohio, Oregon, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the physician investigator based on radiological and/or clinical assessment:
* cT1c, N1-N2
* cT2, N0-N2
* cT3, N0-N2
* cT4a-d, N0-N2
* The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2- as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
* Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory.
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before Cycle1 Day 1 (C1D1).
* Demonstrates adequate organ function.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Metastatic (Stage IV) breast cancer or clinical node stage 3 (cN3) nodal involvement
* Has received any prior treatment, including radiation, systemic therapy,and/or definitive surgery for currently diagnosed breast cancer
* Has undergone excisional biopsy of the primary tumor, axillary lymph node dissection, and/or axillary sentinel lymph node biopsy prior to study treatment.
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before C1D1.
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137).
* Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC).
* Received prior treatment with a topoisomerase I inhibitor-containing ADC.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Known additional malignancy that is progressing or has required active treatment within the past 5 years.
* Uncontrolled systemic disease.
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, has current pneumonitis/interstitial lung disease or has suspected interstitial lung disease (ILD) or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening..
A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer
BNT323/DB-1303, an investigational agent whose mechanism is not explicitly stated in the registry (tested in HER2-expression-selected cohorts), is compared against physician's choice chemotherapy in recurrent endometrial cancer previously treated with platinum chemotherapy and immune checkpoint inhibitors.
NCT06340568 · Phase 3 · BioNTech SE
Recruiting sites: California, Colorado, Connecticut, District of Columbia, Florida, Illinois, Kentucky, Louisiana, Minnesota, Nevada, New York, Ohio, Oklahoma, Pennsylvania, South Dakota, Texas, Utah, Virginia
Read full eligibility criteria
Key Inclusion Criteria:
* Are female adults (defined as ≥18 years of age or acceptable age according to local regulations at the time of voluntarily giving informed consent).
* Have histologically confirmed endometrial cancer that:
* Is recurrent,
* Has a HER2 IHC score of 1+, 2+ (Cohort 1), or 3+ (Cohort 2) as determined by central laboratory testing for HER2 expression, and
* Is not defined as a true sarcoma (i.e., leiomyosarcoma or endometrial stromal sarcoma). Note: Uterine carcinosarcoma is allowed.
* Have measurable disease defined by RECIST v1.1.
* Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
* Have recurrent endometrial cancer and meet any of the following:
* developed recurrence \<12 months from completing platinum-based chemotherapy given as adjuvant therapy for Stage I to III disease, or
* developed recurrence after platinum-based chemotherapy in the recurrent/metastatic setting.
* Have received prior ICI treatment (i.e., anti-programmed death 1/anti-programmed death-ligand 1)
* Have a life expectancy of ≥12 weeks at screening.
Key Exclusion Criteria:
* Are ineligible for all options in the investigator's choice of chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).
* Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior the first dose of study treatment.
* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, or peritoneal shunt within 2 weeks prior to the first dose of study treatment.
* Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent, and topical corticosteroids. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.
* Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior to the first dose of study treatment, severe asthma, chronic obstructive pulmonary disorder with moderate acute exacerbations, restrictive lung disease, pulmonary fibrosis, radiation pneumonitis, significant pleural effusion etc.), or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and/or prior pneumonectomy (complete).
* Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of study treatment.
* Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia, fatigue, or endocrinopathies that are well controlled) not yet resolved to Grade ≤1 or baseline.
* Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.
* Have a history of allergies, hypersensitivities, or intolerance to study treatments (investigational medicinal products and auxiliary medicinal product) including any excipients thereof or to other monoclonal antibodies. Participants who have successfully undergone a desensitization process and are able to tolerate the drug are eligible.
* Had prior treatment with topoisomerase I inhibitors, including ADCs.
* Have left ventricular ejection fraction \<55% by either echocardiography or multiple-gated acquisition within 28 days prior to the first dose of study treatment. This includes participants with tissue doppler E/e' ratio \>15.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer
This is a phase I/II trial testing the HER2-targeted topoisomerase I inhibitor antibody-drug conjugate BNT323 combined with the PD-L1/VEGF-A bispecific antibody BNT327 in patients with locally advanced, unresectable, or metastatic HER2-positive, HER2-low/ultralow/null, or triple-negative breast cancer.
NCT06827236 · Phase 1/2 · BioNTech SE
Recruiting sites: California, Florida, Georgia, Illinois, Michigan, Missouri, New Jersey, New York, Tennessee, Texas
Read full eligibility criteria
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
* Have pathologically documented BC that:
* Is locally advanced, unresectable or metastatic.
* Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
* Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
* Have measurable disease defined by RECIST v1.1.
* Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
Key Exclusion Criteria:
* Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.
* Have received any of the following therapies or drugs prior to the initiation of the study:
* Participants who have received prior treatment with BNT323.
* Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) / vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
* Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer
BNT324, a B7-H3-directed antibody-drug conjugate, is combined with BNT327, a PD-L1/VEGF bispecific antibody, in patients with advanced/metastatic or relapsed/progressive small cell and non-small cell lung cancer across first-line and later-line settings.
NCT06892548 · Phase 1/2 · BioNTech SE
Recruiting sites: Arizona, California, Colorado, Florida, Iowa, Minnesota, New Jersey, New York, Ohio, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Aged ≥18 years at the time of giving informed consent.
* Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study.
* Part 1: Participants with NSCLC and SCLC
* Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L
* Part 2 Cohort 2: Participants with SCLC, 2L+
* Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+
* Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L
* Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+
* Part 2 Cohort 6: Participants with NSCLC AGA positive
* Part 2 Cohort 7: Participants with SCLC, 1L
* Have measurable disease defined by RECIST version 1.1.
* Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have a life expectancy of ≥12 weeks.
Exclusion Criteria:
* Prior treatment with B7-H3 targeted therapy.
* Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting.
* Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment.
* Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.
A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment Pumitamig (BNT327) and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer
BNT314, an EpCAM x 4-1BB bispecific antibody, is being tested in combination with pumitamig (a PD-L1 x VEGF-A bispecific antibody) and chemotherapy in patients with advanced/metastatic MSS/pMMR colorectal cancer.
NCT07079631 · Phase 1/2 · BioNTech SE
Recruiting sites: Connecticut, Michigan, Ohio, Texas
Read full eligibility criteria
Key Inclusion Criteria:
* Have unresectable histologically confirmed adenocarcinoma of the colon or rectum.
* Have confirmed non-microsatellite instability-high (non-MSI-H)/pMMR mCRC per Food and Drug Administration (FDA)/European Commission (EC) approved test or based on local testing.
* Have measurable disease defined by RECIST v1.1.
* Must provide a tumor tissue sample (formalin-fixed, paraffin-embedded or tissue slides) collected before C1D1 for enrollment. A newly obtained tumor sample is preferred. If it is not feasible to obtain a recent tumor sample, participants can provide archival tumor tissue (less than 2 years prior treatment).
* Have Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Have a life expectancy of ≥12 weeks.
* Have an adequate organ and bone marrow function within ≤7 days of Day 1 as defined in the protocol.
* Have had an adequate previous treatment washout period before randomization/enrollment as defined in the protocol.
Inclusion criteria applicable to only protocol-specific cohorts:
* Have histologically confirmed metastatic colorectal cancer and radiographically documented disease progression after ≥2 prior lines of systemic therapy for metastatic disease as defined in the protocol.
* Have progressed following first-line chemotherapy as specified in the protocol.
* Have not received prior systemic therapy for MSS/pMMR mCRC. Participants who received chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease in the neoadjuvant or adjuvant setting are eligible for the study if therapy was completed at least 6 months prior to initiation of study treatment.
Other cohort-specific inclusion criteria apply.
Key Exclusion Criteria:
* Confirmed MSI-H/deficient mismatch repair mCRC (per FDA/CE approved test or based on local testing).
* Prior treatment with epithelial cell-adhesion molecule or 4-1BB targeted or immunotherapy.
* Prior treatment with immune checkpoint inhibitors or programmed death-ligand 1 (PD\[L\]-1)/vascular endothelial growth factor bispecific antibody.
* Is a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment.
* Have uncontrolled or significant cardiovascular disease as specified in the protocol.
* Have left ventricular ejection fraction \<50% by echocardiogram or multigated acquisition within 28 days before randomization/enrollment.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Participants with untreated, asymptomatic brain metastases for whom local therapy is not indicated per SoC may be eligible if neurologically stable and (if deemed necessary by the investigator). Except for brain metastases history, any participants at imminent risk for spinal cord compression or leptomeningeal disease are not eligible.
* Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline toxicities that have resolved with sequelae (e.g., tracheostomy, chronic use of feeding tube, replacement hormones) are allowed, if not associated with increased risk of complications per investigator's assessment.
* Participants in Part B or C who fulfill one of the conditions:
* Prior treatment with anticancer therapies (as defined in the protocol) with unusual toxicity, or
* Known dihydropyrimidine dehydrogenase (DPD) deficiency, testing performed according to the local guidelines. If not tested, lack of DPD activity must be tested for the participants who have not received anticancer therapies (as defined in the protocol) in the prior lines of treatment; testing should be performed according to the local guidelines.
* Have a history of another primary malignancy within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated (adjuvant hormone therapy for malignancies at low risk of relapse is allowed) or have a known additional malignancy that is progressing or requires treatment.
* Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have 24-h urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-h urine protein quantitative test is not required.
* Have active autoimmune disease or a history of autoimmune disease (myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, vasculitis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis) with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency (allogeneic hematopoietic stem cell transplantation or organ transplantation). Participants with protocol-specified conditions may be eligible.
* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, acute gastrointestinal bleeding for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Have evidence of major coagulation disorders or other significant risks of hemorrhage as specified in the protocol.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors
This Phase 1/2 trial evaluates BNT326, a HER3-directed antibody-drug conjugate carrying a topoisomerase I inhibitor payload, given alone or combined with pumitamig (a PD-L1/VEGF-A bispecific antibody), in patients with advanced/metastatic solid tumors, including specific cohorts for previously treated cutaneous melanoma and advanced NSCLC.
NCT07070232 · Phase 1/2 · BioNTech SE
Recruiting sites: Arizona, California, Connecticut, Florida, Georgia, Massachusetts, Michigan, New York, North Carolina, Ohio, Pennsylvania, Texas, Utah, Wisconsin
Read full eligibility criteria
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
* Aged ≥18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older.
* Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease. This requirement may be considered met when advanced disease derives from unequivocal progression of a previously biopsied site of disease (e.g., progression of residual tumor after concomitant chemo-radiation for Stage III NSCLC).
* Have measurable disease defined by RECIST v1.1.
* Have ECOG performance status of 0 or 1.
* Have adequate organ and bone marrow function (as specified in the protocol) within 7 days before randomization/enrollment.
* Cohort 1A:
* Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.
* Participants must have previously received a PD-1 or PD-L1 inhibitor, and, for participants with human gene that encodes a protein called B-Raf (BRAF) gene mutant melanoma, a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene inhibitor with or without mitogen-activated protein kinase protein inhibitor, if available and clinically indicated per local standard of care (SoC) and have experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
* Cohort 1B and 1C: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC.
* Cohort 1B:
* Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC.
* Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.
* Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less.
* Cohort 1C:
* Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
* Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR Tyrosine Kinase Inhibitors (TKI), with at least one being a third-generation EGFR TKI. If there is no third-generation EGFR TKI approved as part of SoC by local health authorities in a certain country, failure/progression on any EGFR TKI is acceptable for eligibility.
* Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
* Prior chemotherapy and amivantamab are permitted only if administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first-line) treatment for advanced/metastatic disease. Participants must not have received any other systemic therapies (such as chemotherapy, immunotherapy, or targeted agents) for advanced/metastatic disease, unless those treatments were given in combination with an EGFR TKI.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
* Cohort 1D:
* Have histologically or cytologically confirmed diagnosis of unresectable or metastatic acral/uveal/mucosal melanoma not amenable to local therapy.
* Participants must have:
* Previously been treated with a PD-1 or PD-L1 inhibitor, if clinically indicated and available per local SoC, and/or
* For participants with Human Leukocyte Antigen Alleles (HLA-A)\*02:01 serotype-positive disease (only applicable for uveal melanoma), previously been treated with tebentafusp-tebn if clinically indicated and available per local SoC, and
* Experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
* Cohorts 1E and 1F (DDI):
* Have histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced solid tumor not amenable to ablative or curative approach including, but not limited to:
* Cholangiocarcinoma, including tumors of the intra- and extrahepatic biliary tract and gallbladder
* Hepatocellular carcinoma (HCC).
* Renal cell carcinoma
* Endometrial carcinoma, excluding those classified as true sarcomas
* Pancreatic ductal adenocarcinoma (PDAC) (see below other related inclusion criterion)
* Neuroendocrine tumor of pancreatic, gastrointestinal, lung, and thymus that is well differentiated, Grade 1 to 3.
* NSCLC (Cohort 1F only)
* Have experienced disease progression on at least one and no more than three lines of prior therapy or, for Cohort 1E only, discontinued from prior therapy due to intolerance.
* (For participants with PDAC only) Have received one or two lines of systemic therapy for metastatic tumors, and have experienced progression or intolerance to the treatment during or following therapy.
* Cohort 2A: Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.
* Cohort 2B: Have histologically or cytologically confirmed diagnosis of recurrent unresectable or metastatic breast cancer that is documented as HER2-negative and either HR-negative or HR-positive per American Society of Clinical Oncology/College of American Pathologists guidelines.
* Cohort 2D:
* Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous-cell carcinoma is excluded).
* (2L subgroup): Had disease progression during or after one prior line of anti-cancer therapy for recurrent/metastatic disease.
* (3L subgroup): Has received two or more lines of prior anti-cancer therapy for recurrent/metastatic disease.
* (HER2-expression positive subgroup): Has received at least one prior line of systemic therapy for recurrent or metastatic disease, including a HER2-targeted agent in accordance with local SoC.
* Cohort 2E:
* Histologically and/or cytologically documented recurrent unresectable metastatic colorectal adenocarcinoma.
* Must have received at least one line to a maximum of three lines of prior SoC treatment for recurrent/metastatic disease.
* Cohort 1G and 2F:
* Histologically and/or cytologically documented recurrent unresectable metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology.
* Must have received platinum-based chemotherapy, with or without an anti-PD-(L)1 agent and bevacizumab for metastatic/recurrent disease, unless the patient is not a candidate in the opinion of the treating physician.
Key Exclusion Criteria (applicable to all participants and all parts unless otherwise specified):
* Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (e.g., severe diarrhea).
* Have an uncontrolled concomitant or intercurrent illness that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events, including:
* Bleeding diathesis or active hemorrhage,
* Active infection,
* Child-Pugh class B or C cirrhosis,
* Known pulmonary disease with significant impact in lung function
* Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies),
* Psychiatric or abuse condition
* Infectious colitis Grade ≥2 not resolved to Grade 1 within 72 hours within the past 3 months.
* Have LVEF \<50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
* Are a participant of child-bearing potential who are pregnant or breastfeeding or are planning pregnancy within 225 days (\~7.5 months) after receiving last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer.
* Are potentially fertile males, who are planning to father children during the study or within 135 days (\~4.5 months) after the last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer.
* Are subject to exclusion periods from another investigational study.
* Specific to pumitamig: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.
* Specific to pumitamig: Have a history of intolerance to treatment with an anti-vascular endothelial growth factor, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.
* Cohort 1E: Have histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
A Clinical Trial Evaluating the Safety of TD001 In Patients With PSMA-Expressing Metastatic Prostate Cancer
TD001 is a PSMA-targeted antibody-drug conjugate being studied in men with metastatic castration-resistant prostate cancer previously treated with an androgen receptor pathway inhibitor.
NCT07258407 · Phase 1/2 · T.O.A.D. Oncology SA
Recruiting sites: Connecticut
Read full eligibility criteria
Inclusion Criteria:
* Patient must fully understand the study requirements and voluntarily sign informed consent.
* PSMA-expressing metastatic CRPC with documented progression based on serum PSA, RECIST 1.1 with PCWG3, and/or bone disease.
* At least one measurable metastatic lesion per RECIST 1.1.
* Adequate organ function.
* Prior orchiectomy and/or ongoing androgen deprivation therapy.
* Prior treatment with at least one androgen receptor pathway inhibitor (ARPI) drug.
Exclusion Criteria:
* Previous treatment with strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, or hemi-body irradiation, within 6 months before treatment.
* Systemic anticancer therapy including an investigational agent within 28 days before treatment.
* Known hypersensitivity to the components of TD001, its analogs, or excipients.
* Current dyspnea at rest, other disease requiring continuous oxygen therapy, or history of pneumonitis
A Clinical Trial of Adjuvant Intismeran (V940) With or Without Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) in High-Risk Stage I Non-Small Cell Lung Cancer (V940-014)
Intismeran (V940), an individualized mRNA neoantigen cancer vaccine, is being studied as adjuvant therapy with or without subcutaneous pembrolizumab/berahyaluronidase alfa versus placebo in resected high-risk Stage I non-small cell lung cancer.
NCT07513376 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: California, Colorado, Connecticut, Florida, Illinois, Missouri, Montana, Nebraska, Nevada, New York, North Carolina, North Dakota, Pennsylvania, South Dakota, Tennessee, Virginia, West Virginia, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histological diagnosis of pathological Stage I (tumor ≤4 cm) non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) 9th Edition with at least 1of the following high-risk pathologic features as assessed locally: tumor size \>2cm, visceral pleural invasion, lymphovascular invasion, or high-grade histology
* Has undergone a complete surgical resection of the primary NSCLC
* Has not received other prior treatment outside of definitive surgery (including but not limited to chemotherapy, immunotherapy, targeted therapy, or radiotherapy) for their current Stage I NSCLC
* Has provided a tissue sample from recent surgery along with the required blood sample
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has diagnosis of any 1 of the following: small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, neuroendocrine tumor with large cell components, sarcomatoid carcinoma, or two synchronous primary NSCLCs
* Has any clinically significant cardiovascular disease within 12 months before randomization, including a history of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), valvular heart disease requiring surgical intervention, New York Heart Association Class III-IV heart failure, unstable angina, myocardial infarction (MI), pulmonary hypertension, cardiovascular accident (CVA), or hemodynamically unstable cardiac arrhythmia
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Hormonal supplementation (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy other than those permitted in protocol
* Has history of stem cell/solid organ transplant
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications
A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015)
Calderasib (MK-1084), an oral KRAS G12C inhibitor, is being studied in combination with the PD-L1 inhibitor durvalumab versus placebo plus durvalumab as consolidation therapy after chemoradiotherapy in unresected, KRAS G12C-mutant, locally advanced (stage II-III) non-small cell lung cancer.
NCT07554339 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Illinois, Nebraska, New York, North Carolina, Virginia
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histological or cytological diagnosis of locally advanced, unresected Stage II (node-positive) to III non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology.
* Has completed definitive platinum-based concurrent chemoradiotherapy (CCRT) prior to enrollment, without disease progression.
* Has provided a tumor tissue sample for central laboratory testing of Kirsten rat sarcoma G12C (KRAS G12C) status, programmed cell death ligand 1 (PD-L1) status, and biomarker research.
* Tumor tissue sample has a demonstrated presence of KRAS G12C mutation and an evaluable PD-L1 status result.
* If human immunodeficiency virus (HIV)-infected, has well-controlled HIV on antiretroviral therapy (ART).
* If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral therapy.
* If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
* Has a body weight ≥35 kg.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has a diagnosis of small cell lung cancer or mixed tumors with small cell elements.
* Has a gastrointestinal disorder affecting absorption or is unable to swallow orally administered medication.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease.
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
* Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has received prior treatment (other than definitive CCRT) for NSCLC.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* Has a history of, or has current, (noninfectious) pneumonitis/interstitial lung disease that required/requires steroids.
* Has an active infection requiring systemic therapy.
* Has a history of stem cell/solid organ transplant.
* Has not adequately recovered from major surgery or has ongoing surgical complications.
A Clinical Trial of Sac-TMT in People With Non-HRD Positive Advanced Ovarian Cancer (MK-2870-021)
Sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate, is studied with or without bevacizumab as maintenance therapy versus standard care in non-HRD-positive advanced ovarian, primary peritoneal, or fallopian tube cancer following first-line platinum-based chemotherapy.
NCT07318558 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: Alabama, California, Florida, Georgia, Illinois, Indiana, Louisiana, Maine, Maryland, Nebraska, Nevada, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, Tennessee, Virginia
Read full eligibility criteria
The main inclusion criteria include but are not limited to the following:
* Has diagnosis of FIGO 2014 Stage III or Stage IV, histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with one of the following histologies: high-grade serous, high-grade endometrioid, clear cell carcinoma, or malignant mixed Müllerian tumour with a high-grade serous component. Tumors reported as Grade 2 may be enrolled only if predominately (\>50%) Grade 3 features are present.
* Has completed primary debulking surgery or interval debulking surgery.
* Has completed first-line (1L) platinum-based chemotherapy, with a response of stable disease, partial response, complete response or no evidence of disease per protocol.
* Has provided tumor tissue that is not previously irradiated.
* Has well-controlled human immunodeficiency virus (HIV) on antiretroviral therapy if diagnosed with HIV
* Has undetectable hepatitis B virus (HBV) viral load and received HBV antiviral therapy if hepatitis B surface antigen (HBsAg)-positive.
* Has undetectable hepatitis C virus (HCV) viral load if has a history of HCV infection.
The main exclusion criteria include but are not limited to the following:
* Has nonepithelial cancers, low-grade serous tumors, low-grade endometrioid tumors, borderline tumors mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor, and undifferentiated carcinoma.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has a history of severe eye disease.
* Has active inflammatory bowel disease requiring immunosuppressive medication or a previous history of inflammatory bowel disease.
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD), which required steroids, has current pneumonitis/ILD, or has suspected ILD, or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening.
* Received prior systemic anticancer therapy, with the exception of the first-line platinum-based chemotherapy required by the inclusion criteria.
* Had a live or live-attenuated vaccine within 30 days of randomization.
* Has a known additional malignancy that is progressing or required active treatment within the past 3 years.
* Has active infection requiring systemic therapy.
* Has concurrent and active HBV and HCV infections.
* Has HIV infection and a history of Kaposi's sarcoma and/or multicentric Castleman's disease.
* Has not recovered from major surgery or has ongoing surgical complications.
* Has a homologous recombination deficiency (HRD)-positive, unknown, or inconclusive tumor status as determined by the central laboratory.
* Active or ongoing stomatitis of any grade.
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031)
Sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, is compared to non-platinum chemotherapy (vinflunine, docetaxel, or paclitaxel) in previously treated locally advanced or metastatic urothelial cancer.
NCT07419295 · Phase 3 · Merck Sharp & Dohme LLC
Recruiting sites: District of Columbia, Georgia, Maryland, Massachusetts, Michigan, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has histologically documented locally advanced/metastatic urothelial cancer. Locally advanced disease must not be amenable to resection or radiation with curative intent per investigator assessment
* Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the investigator
* Has received treatment with anti-programmed cell death \[ligand\] 1 (anti-PD-\[L\]1) therapy, platinum-based chemotherapy, and enfortumab vedotin (EV)
* Prior therapy with disitamab vedotin (DV) is allowed but will not meet the requirement for prior treatment with EV, except in China, where participants may have received DV instead of EV before study entry
* Has received a maximum of 2 prior lines of therapy
* Has experienced radiographic disease progression on or after the immediate prior line of therapy before study entry
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
* Is eligible to receive at least one of the control arm nonplatinum chemotherapy options (paclitaxel, docetaxel, or vinflunine)
* Is able to provide archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated
* If human immunodeficiency virus (HIV) positive, has well-controlled HIV on antiretroviral therapy (ART)
* If hepatitis B surface antigen (HBsAg) positive, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load
* If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load
* Has adequate organ function
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from adverse event (AE) associated with anticancer therapy
* Has received prior therapy with trophoblast cell-surface antigen 2 (TROP2)-targeted antibody drug conjugate (ADC)
* Has received prior therapy with a topoisomerase 1 inhibitor-containing ADC
* Has completed prior external radiotherapy within 6 weeks or stereotactic radiotherapy within 4 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
* Has received prior chemotherapy for urothelial cancer with any of the study therapies in the control arm (paclitaxel, docetaxel, and vinflunine)
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has a current or past history of central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring systemic therapy other than those permitted per protocol
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery, or has ongoing surgical complications
A Clinical Trial to Assess PVX7 Immunotherapy Regimens in Advanced Cervical Cancer Patients
PVX7 is a therapeutic prime/boost cancer vaccine (DNA prime plus vaccinia-vectored boost) targeting HPV16/18 E6/E7 oncoproteins, studied as post-primary-therapy maintenance immunotherapy in advanced HPV-positive cervical cancer patients with no evidence of residual disease.
NCT06315257 · Phase 1 · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting sites: Alabama, Maryland
Read full eligibility criteria
Inclusion Criteria:
* Female subjects age 18 years or older with diagnosis of advanced (stage IB1-IVA) HPV+ cervical cancer and have completed primary treatment (consisting of any of the following as per NCCN guideline standard of care: surgical resection, radiation, and/or platinum-based chemotherapy) within the past 12 months.
Patients who are recommended to receive anto-PD-1 or anti-PD-L1 therapy after chemoradiation are eligible to enroll and can continue to receive such therapy while receiving study drug.
* No history of or current evidence of residual disease or disease recurrence based on imaging and clinical assessments within 8 weeks of enrollment
* HIV uninfected
* Hepatitis B surface antigen negative
* Anti-hepatitis C (HCV) antibody negative or negative HCV polymerase chain reaction (PCR)
* Patients who are able and willing to comply with all study procedures and voluntarily sign an informed consent form
* Adequate organ function as defined by the following parameters:
* white blood cell count ≥ 3,000 cells/cu mm
* lymphocyte number ≥ 500 cells/cu mm
* absolute neutrophil count ≥ 1,000 cells/cu mm
* platelets ≥ 90,000/cu mm
* hemoglobin ≥ 9 g/dL
* total bilirubin \<1.5 X upper limit of normal (ULN), \<3 x ULN if Gilbert's disease
* Aspartate Transferase(AST) and Alanine Transaminase (ALT) \<3 X ULN
* creatinine \< 1.5 X ULN or estimated creatinine clearance ≥ 60 ml/min per Modified Cockcroft-Gault Formula
* Eastern Cooperative Oncology Group performance status of 0 or 1
* All clinically significant toxicities related to prior therapy should be less than or equal to Grade 1 at time of enrollment
* Ability and willingness for one month post vaccination to follow vaccine inoculation site care and avoid close social contact with children under 1 year old or close social or domestic contact with a pregnant woman or individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, or immunodeficiency states including HIV infection
Exclusion Criteria:
* Women of child-bearing potential (i.e., those who have had fertility-sparing procedures for the management of cervical cancer) will be excluded unless agreed to remain sexually abstinent or have a partner who is sterile (i.e. vasectomy), or use methods of contraception (e.g., oral contraception, barrier methods, spermicide, intrauterine device (IUD)), throughout the first 6 months of the study.
* Because there is a risk for adverse events in nursing infants, breastfeeding must be discontinued if the mother is treated on study.
* Diagnosed with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients diagnosed with acquired, hereditary, or congenital immunodeficiencies
* Diagnosis with a medical condition that requires systemic treatment with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), alkylating agents, antimetabolites, radiation, Tumor Necrosis Factor (TNF) inhibitors, or systemic corticosteroids, either chronically or within 30 days of first PVX7 vaccination.
* Administration of any blood product within 30 days of signing informed consent.
* Need for ongoing therapeutic anticoagulation during the study period due to concern for increased risk of bleeding.
* Previous severe allergic reaction or hypersensitivity to a vaccine or any of its components
* Participation in a study with an investigational compound or device within 30 days of signing informed consent
* Known active central nervous system disease
* Surgery within 30 days of first PVX7 vaccination, excluding minor procedures
* Diagnosis with an uncontrolled intercurrent illness including, but not limited to, ongoing, or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* Diagnosis with an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis)
* History of myocarditis or pericarditis.
* Known underlying heart disease (e.g., cardiomyopathy, congestive heart failure, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction or cerebrovascular accident within the past 6 months).
* Patients and the patients close social, sexual, or domestic contacts may not have non-healed wounds or active exfoliative skin conditions such as: Eczema, Burns, Impetigo, Varicella-zoster virus infection, Herpes simplex virus infection, Severe acne, Severe diaper dermatitis with extensive areas of denuded skin, Psoriasis, Lichen planus, Darier disease (keratosis follicularis).
* History or presence of atopic dermatitis
* Inability or unwillingness to for one month post vaccination follow vaccine inoculation site care and avoid social contact with children under 1 year old or close social or domestic contact with a pregnant woman or individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, or immunodeficiency states including HIV infection
A Clinical Trial to Evaluate EDV Nanocell Therapy With Gemcitabine and Nab-paclitaxel in Pancreatic Cancer
E-EDV-D682 (an EGFR-targeted bacterial nanocell delivering the anthracycline PNU-159682) plus EDV-GC (a nanocell delivering the immunoadjuvant alpha-galactosylceramide) is being tested in combination with gemcitabine and nab-paclitaxel versus gemcitabine/nab-paclitaxel alone in second-line metastatic pancreatic ductal adenocarcinoma after progression on FOLFIRINOX/NALIRIFOX.
NCT07049055 · Phase 1/2 · Engeneic Pty Limited
Recruiting sites: California, New Jersey, New York, Ohio
Read full eligibility criteria
Inclusion Criteria:
* Histological or pathological confirmation of metastatic pancreas adenocarcinoma. Cytological or histological evidence of metastatic disease is required.
* Male or Female greater than or equal to 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
* Life expectancy ≥ 3 months in the opinion of the Investigator.
* Measurable disease as per iRECIST criteria.
* Subjects must have tumors that express EGFR.
* Documented disease progression with first line FOLFIRINOX or NALIRIFOX therapy, during or within 3 months (+/- 15 days) after end of therapy.
* No more than one line of prior systemic therapy for metastatic PDAC allowed.
* Albumin level \> 3.0 g/dl
* Adequate hematological function.
* Adequate renal function.
* Adequate hepatic function.
* Adequate cardiac function with LVEF ≥ 50% at baseline.
* Reproductive criteria as follows:
* Female subjects who are of non-reproductive potential
* Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days of the first dose.
* Female subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration.
* Male subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration.
* All study subjects must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration.
* The subject (or subject's legally authorized representative) has provided voluntary signed informed consent.
* According to the investigator's assessment, subject will be able to comply with the study protocol.
Exclusion Criteria:
* Subjects currently receiving any other investigational agent.
* Unresolved (≥ Grade 1) non-hematological adverse events from prior anti-cancer therapy that is not controlled on maximal supportive therapy.
* Significant pericardial effusions, pleural effusions, or ascites that requires intervention. Subjects who require drainage within the last four weeks are ineligible.
* History of leptomeningeal or brain/CNS metastases.
* Ongoing treatment for other malignancies (hormone therapy acceptable).
* Patient may not have a history of malignancy other than PDAC within two years prior to screening except in circumstances where the risk of recurrence, metastasis or death in 5-years is \<10%.
* Concurrent unstable diabetes mellitus or other contraindications for the use of corticosteroids that requires active titration of insulin.
* Subject has experienced a history of uncontrolled coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association \> Class II)
* Uncontrolled hypertension (systolic \> 180 mmHg or diastolic \> 100 mmHg) within two weeks.
* Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy within the last four weeks.
* Baseline QTcF ≥ 450 ms (males) or ≥ 470 ms (females).
* Uncontrolled HIV infection. Patients without a prior diagnosis of HIV infection will undergo HIV testing unless not permitted to do so under local regulations. Patients with known HIV who have controlled infection (viral load undetectable and a CD4 count \>350 either spontaneously or on a stable antiviral regimen) are permitted.
* Uncontrolled Hepatitis B virus (HBV) infection (chronic or acute).
* Uncontrolled Hepatitis C virus (HCV) infection.
* Uncontrolled arterial or venous thrombosis.
* Active or uncontrolled severe infection.
* Uncontrolled hypercalcemia (\>2.6mmol/L or \>10.3mg/dL) or symptomatic hypercalcemia requiring continued treatment for hypercalcemia.
* Received the following procedures within 21 days to receiving their first dose (or has not recovered from the toxic effects of such therapy) including:
* other investigational therapy
* radiotherapy
* any major surgery.
* Prior other therapies or procedures prior to receiving their first dose:
* QTc interval prolonging medicines should be reviewed and where possible their use should be minimized and alternate medicines that are not QTc interval prolonging, considered as substitutes.
* Known allergy/hypersensitivity to investigational components or excipients (trehalose, monoclonal antibody infusions, interferon therapy, or ciprofloxacin HCl (or other quinolones).
* Female who is pregnant or breastfeeding.
* Subject who cannot comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator's knowledge.
* Any kind of disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
* History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC)
This trial evaluates the combination of BNT326 and pumitamig (BNT327/PM8002), two investigational agents whose mechanisms of action are not stated in the registry, as IV infusion therapy in adults with advanced/metastatic non-small cell lung cancer who are either treatment-naïve or have relapsed/progressed after prior systemic therapy.
NCT07111520 · Phase 1/2 · BioNTech SE
Recruiting sites: California, Connecticut, District of Columbia, Florida, Massachusetts, Michigan, New York, Ohio, Texas, Virginia
Read full eligibility criteria
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
* Aged ≥18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older.
* Have measurable disease defined by RECIST v1.1.
* Have Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have adequate organ and bone marrow function within 7 days before randomization/enrollment as defined in the protocol.
* Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC.
Cohort-specific inclusion criteria
Part 1, 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.)
* for AGA-negative NSCLC only:
* Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase (ALK) gene rearrangements, or other genomic alterations for which targeted molecular therapies are available.
* Have experienced relapse or progression during or after treatment with standard systemic therapy in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.
* Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, prior chemotherapy treatment must be limited to 2 lines or less.
* for AGA-positive NSCLC only (excluding EGFR activating mutation):
* Have documented positive test results for one or more actionable genomic alteration: EGFR (other than activating mutations), ALK, ROS proto-oncogene 1 (ROS1), gene encoding the hepatocyte growth factor receptor (MET), human gene that encodes a protein called B-Raf (BRAF), rearranged during transfection (RET), neurotrophic tropomyosin-receptor kinase (NTRK), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), or other genomic alteration with available targeted therapy.
* Must have received at least one prior systemic therapy for advanced disease, which must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other alterations for which targeted therapies are available as a part of local SoC.
* Participants may have received between 1 to 3 lines of systemic treatment of anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. These treatments may be administered concurrently (including with tyrosine kinase inhibitor \[TKI\]) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
* for AGA-positive NSCLC only (with EGFR activating mutation):
* Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
* Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.
* Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
* Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Part 2a (Cohort A), 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.)
* for AGA-positive NSCLC only, excluding EGFR activating mutation:
* Have documented positive test results for one or more actionable genomic alterations: EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations, with available targeted therapy.
* May have received 1 to 4 lines of systemic treatment, of which one prior systemic therapy for advanced disease must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations for which targeted therapies are available as part of local SoC.
* Other therapies may include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently/in combination (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
* for AGA-positive NSCLC only, with EGFR activation mutation:
* Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
* Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.
* Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
* Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Part 2a (Cohort B), 1L, squamous or non-squamous NSCLC, AGA-negative, any PD-L1
* Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
* Have received no systemic anti-cancer treatment in the advanced/metastatic setting. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting.
Part 2b (Cohort C), 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1
* for AGA-negative NSCLC only:
* Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
* Participants should have received 1 to 4 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents.
* Regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.
* for EGFR-sensitizing mutation NSCLC only:
* Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
* Have received 1 or 2 prior systemic therapies for advanced and/or metastatic disease with an approved EGFR TKI, which must include one third-generation anti-EGFR TKI.
* Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
* Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
* May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have experienced disease progression on or after EGFR TKI treatment administered in the advanced/metastatic setting.
* Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Part 2b (Cohort D1) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50% and Part 2b (Cohort D2) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%
* Have no actionable genomic alterations, such as EGFR mutations (Cohort D1)/EGFR-sensitizing mutations (Cohort D2), ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
* Have not received prior systemic therapy for advanced and/or metastatic disease. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting.
Key Exclusion Criteria (applicable to all participants and all parts):
* Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
* Have an uncontrolled concomitant or intercurrent illness, that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring AEs, including:
* Bleeding diathesis or active hemorrhage
* Clinically significant active infection, including respiratory viral infection
* Child-Pugh class B or C cirrhosis
* Known pulmonary disease with significant impact in lung function and/or with potential risk of severe infection
* Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies)
* Psychiatric or abuse condition
* Infectious colitis Grade ≥2 not resolved to Grade 1 within 72 h within the past 3 months
* Have left ventricular ejection fraction \<50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
* Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
* Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
* Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
* Are subject to exclusion periods from another investigational study.
* Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have urine protein ≥2+ and 24-hour urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-hour urine protein quantitative test is not required.
* Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.
* Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria.
* Have active or chronic clinically significant corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9
BNT329, a CA19-9-targeting monoclonal antibody, is being studied as an IV infusion in a phase 1/2 trial for advanced/metastatic CA19-9-expressing solid tumors (pancreatic, biliary tract, urothelial, colorectal, esophagogastric, gastric, endometrial, and epithelial ovarian cancers) that have progressed after standard therapy.
NCT07186842 · Phase 1/2 · BioNTech SE
Recruiting sites: Colorado, Florida, Michigan, New York
Read full eligibility criteria
Key Inclusion Criteria
All participants and parts:
* Have an Eastern Cooperative Oncology Group performance score of 0 to 1
* Have measurable disease per RECIST v1.1, except for ovarian cancer where participants will be evaluated according to Gynecologic Cancer InterGroup criteria.
* Have a life expectancy of ≥3 months in the opinion of the investigator.
* Have adequate organ, coagulation, and hematologic function as defined in the protocol.
Parts A, B, and C:
* Have a histologically confirmed advanced/metastatic tumor type that is known to express CA19-9: PDAC, carcinoma of the bile ducts, invasive urothelial carcinoma of the bladder and urinary tract, colorectal adenocarcinoma, adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, endometrial carcinoma, and epithelial ovarian cancer (including adenocarcinoma of the fallopian tube and peritoneal epithelial cancer \[except mesothelioma\]).
* Have no available standard of care therapy likely to confer clinical benefit in the opinion of the investigator. Participants must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the Food and Drug Administration, American Society of Clinical Oncology, European Society for Medical Oncology, or local guidelines used at the site), and failed at least first-line standard of care therapy prior to enrollment.
Part D:
* Have a histologically confirmed diagnosis of PDAC.
* Must have been offered all available standard therapies including targeted therapies based on mutation status. Established second-line therapies available must not be withheld.
* Have radiographic disease progression and no available standard of care therapy likely to confer clinical benefit in the opinion of the investigator.
Key Exclusion Criteria
All participants and parts:
* Are enrolled in another investigational study or are subject to exclusion periods from another investigational study.
* Have had an inadequate washout period for prior anticancer treatment prior to the first dose of investigational medicinal product (IMP) as defined in the protocol.
* Have received systemic steroids (\>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks prior to the first dose of IMP. The following are exceptions to this criterion:
* Inhaled sprays, topical steroids, or local steroid injections (e.g., intra-articular injection).
* Systemic steroids at physiological doses as replacement therapy (e.g., physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency).
* Steroids as pre-medication for hypersensitivity reactions (e.g., computed tomography (CT) scan pre-medication).
* Have received any live vaccine within 4 weeks prior to the first dose of IMP or intend to receive a live vaccine during the study.
* Have brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anticonvulsants for at least 2 weeks prior to the first dose of IMP.
* Have a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Have active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation in the opinion of the treating investigator.
* Have an active infection that requires systemic therapy within 1 week prior to the first dose of IMP. Participants receiving prophylactic anti-infective therapy (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) may be eligible after discussion with the sponsor.
* Have unresolved toxicities from previous anticancer therapy as defined in the protocol.
NOTE: Other protocol defined inclusion/exclusion criteria apply.
A Comparison of Radical Prostatectomy and Precision Prostatectomy in Low- and Intermediate-risk Prostate Cancers.
This trial compares precision prostatectomy, a nerve- and tissue-sparing surgical technique, against standard radical prostatectomy in patients with low- and intermediate-risk localized prostate cancer.
NCT07348367 · Phase N/A · Henry Ford Health System
Recruiting sites: Michigan
Read full eligibility criteria
Inclusion Criteria:
* Prostate cancer patients receiving treatment at Henry Ford Health from the investigator or co-investigator who opt for surgery.
* Prostate-specific antigen (PSA) ≤20 ng/mL
* Clinical stage ≤cT2
* Dominant unilateral lesion with Gleason ≤4+3 on biopsy
* No Gleason ≥4 contralaterally
* Preoperative SHIM score ≥17 (with or without phosphodiesterase-5 inhibitor use)
Exclusion Criteria:
* • Androgen deprivation therapy within 6 months.
* Nodal positive disease
* Metastatic disease
* Prior prostate cancer therapy (e.g., radiation, HIFU).
* Significant comorbidities precluding surgery or life expectancy \<5 years as defined by the Prostate Cancer Comorbidity Index \[5\].
* Any previous cancer diagnosis.
A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas.
ONM-501, an intratumoral STING agonist (PC7A polymer micelle loaded with cGAMP), is being studied alone and combined with the PD-1 inhibitor cemiplimab in patients with advanced, unresectable or recurrent solid tumors and lymphomas lacking standard therapy options.
NCT06022029 · Phase 1 · OncoNano Medicine, Inc.
Recruiting sites: California, Florida, Ohio, Pennsylvania, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Ability to understand and willingness to sign written informed consent before performance of any study procedures
2. Age ≥ 18 years
3. Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
4. Participants must have a minimum of one injectable and measurable lesion.
5. Participants with prior Hepatitis B or C are eligible if they have adequate liver function
6. Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load \<400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
7. Adequate bone marrow function:
8. Adequate liver function
Exclusion Criteria: Patients will be excluded from this study if they meet any of the following criteria (Part 1a and Part 1b).
1. Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
2. Major surgery within 4 weeks before the first dose of study drug.
3. Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
4. Prolongation of corrected QT (QTc) interval to \>470 millisecond (ms) for males and females when electrolytes balance is normal.
5. Females who are breastfeeding or pregnant at screening or baseline
6. Females of childbearing potential that refuse to use a highly effective method of contraception.
7. Has uncontrolled or poorly controlled hypertension as defined by a sustained BP \> 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
8. Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
9. Has an active infection requiring systemic treatment
10. Is participating in another therapeutic clinical trial
Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
1. Has known hypersensitivity to any component in the formulation of cemiplimab
2. Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily prednisone equivalent)
3. Has a condition requiring systemic treatment with corticosteroids
A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER)
Sarilumab, an agent whose mechanism is not stated in the registry, is combined with capecitabine chemotherapy and studied in HER2-negative metastatic breast cancer (Phase 1) and in stage I-III triple-negative breast cancer with high-risk residual disease after neoadjuvant therapy (Phase 2).
NCT04333706 · Phase 1/2 · University of Southern California
Recruiting sites: California, Florida
Read full eligibility criteria
Inclusion Criteria:
* A. Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures.
* B. Both males and females ≥ eighteen years of age
* C. A clinical diagnosis of metastatic triple negative or hormone resistant, Her2/neu-negative breast cancer that has been confirmed histologically at one point during the course of the disease. TNBC is defined as ER/PR IHC positivity rate of \<10% and Her2Neu-negative (Phase I only)
* D. A life expectancy of at least 6 months. (Phase I only)
* E. Any previous cytotoxic chemotherapy must have been a minimum of 3 weeks prior to study drug administration. There is no limit on the number of prior therapies. For ER/PR-positive tumors, endocrine therapy must have been included in at least one of those prior regimens. Prior capecitabine is allowed only if not given in the treatment regimen immediately prior to the enrollment in this study. (Phase I only)
* F. A diagnosis of TNBC confirmed histologically and defined as ER/PR IHC positivity rate of \<10% and Her2/neu-negative. (Phase II and Parallel Baseline Arm only)
* G. A pathologic confirmation of stage I, or II, or III breast cancer with less than a complete pCR, defined as the absence of residual invasive cancer in resected breast specimen and sampled lymph nodes with residual noninvasive cancer or in situ disease allowed. (Phase II and Parallel Baseline Arm only)
* H. Must not have received prior systemic treatment for breast cancer except for those included in the neoadjuvant regimen and the neoadjuvant regimen must not have included capecitabine nor sarilumab. (Phase II and Parallel Baseline Arm only)
* I. An ECOG Performance Status ≤2.
* J. Adequate organ function defined as:
1. Absolute neutrophil count (ANC) \> 1500/mcl (use of G-CSF is allowed)
2. Platelets ≥ 100,000/mcl
3. Hemoglobin ≥ 9 (pRBC +/- ESA are allowed)
4. ALT ≤ 5 x ULN
5. AST ≤ 5 x ULN
6. Bilirubin ≤ 3 x ULN
7. GFR ≥ 30 ml/min
* K. Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
* L. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
Exclusion Criteria:
* A. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug.
* B. Females who are pregnant or breastfeeding.
* C. History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
* D. Hepatitis B infection except for prior vaccination. (Phase I and Phase II only).
* E. Known history of tuberculosis injection. (Phase I and Phase II only).
* F. A history of diverticulitis. (Phase I and Phase II only).
* G. Use of live vaccines within 30 days prior to study treatment due to the risk of infection. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella (MMR), varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. (Phase I and Phase II only)
* H. History of other malignancy that in the primary oncologist's estimation has at the time of study participation a higher risk of recurrence or death than the study-related cancer.
* I. Prisoners or subjects who are involuntarily incarcerated.
* J. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
* K. Subjects demonstrating an inability to comply with the study and/or follow-up procedures.
A Dose Randomization Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated With ADCs
Bulumtatug fuvedotin, a nectin-4-directed antibody-drug conjugate carrying the MMAE payload, is being tested at two dose levels in patients with recurrent or metastatic triple-negative breast cancer previously treated with a taxane and a topoisomerase-inhibitor-based ADC.
NCT06908928 · Phase 1 · Mabwell (Shanghai) Bioscience Co., Ltd.
Recruiting sites: California, Colorado, Illinois, Massachusetts, New York, Tennessee
Read full eligibility criteria
Inclusion Criteria
* Patient has measurable disease by RECIST v1.1
* Recurrent or metastatic triple-negative breast cancer patients as per current ASCO/CAP guidelines
* Patient has received prior treatment with a taxane and an antibody-drug conjugate with a topoisomerase inhibitor payload.
* Patient has received no more than 3 prior lines of cytotoxic therapy in the locally advanced or metastatic setting.
* Provision of archival tumor tissue or fresh tumor biopsy.
* Capable of giving informed consent
* Male or female subjects aged ≥ 18 years.
* Subjects must be willing to receive blood transfusions if medically indicated.
* ECOG 0-1
* Adequate hematologic and organ function
* Life expectancy of at least 3 months as assessed by the investigator
* Compliance with contraceptive requirement
Exclusion Criteria:
* Have received any prior treatment with enfortumab vedotin, tisotumab vedotin or other MMAE based or nectin-4 targeted antibody-drug conjugates.
* Unstable CNS metastasis requiring treatment in the last 28 days.
* Acute infection requiring IV treatment in the last 14 days.
* Grade ≥2 peripheral neuropathy.
* Pregnant or breastfeeding women.
* Life-threatening illness or uncontrolled medical conditions that could compromise the subject's safety or put the study outcomes at risk
* Any systemic anticancer therapy in the last 28 days prior to first administration of study drug.
* Active HCV, HBV or HIV infection unless well controlled with anti-viral therapy.
* Active or chronic corneal disorder, keratitis, corneal ulcerations or Sjogren's syndrome.
* Have any ongoing acute inflammatory skin disease or chronic skin disease not well controlled.
* Have been diagnosed with another primary malignancy except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or subjects with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
* Have significant, uncontrolled or active cardiovascular disease
* Have active or a history of pneumonitis or interstitial lung disease that requires corticosteroid treatment. Patients with radiation pneumonitis that does not require treatment is allowed.
* Have uncontrolled diabetes.
* Have received any strong CYP3A4 inhibitors within 14 days prior to the first dose of study drug.
* Subjects known to be hypersensitive to bulumtatug fuvedotin or to any components of the formulation.
* History of drug abuse including narcotic and psychiatric drugs within 12 months prior to screening.
* Have received a live vaccine within 30 days of planned start of study therapy.
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
This trial administers a tetanus-diphtheria or polio booster vaccine (as an immune-recall strategy) alongside standard-of-care PD-1 (± anti-CTLA-4) checkpoint inhibitor therapy in patients with advanced metastatic melanoma.
NCT05077137 · Phase 1 · Duke University
Recruiting sites: North Carolina
Read full eligibility criteria
Inclusion Criteria:
1. Histologically confirmed advanced metastatic melanoma
2. Male or female participants who are at least 18 years of age on the day of signing informed consent
3. Participants must be planned or scheduled by their treating physician to receive PD-1 therapy or PD-1 plus anti CTLA-4 therapy as standard of care
4. Participant (or legally acceptable representative if applicable) provides written informed consent for the trial
5. Participant must have at least 1 lesion that is at least 8 mm in size and is cutaneous, subcutaneous, palpable, or amenable to ultrasound guided core biopsy. The lesion chosen for biopsy can also be a target lesion but does not have to be a target lesion
6. Adequate organ function as defined below. Standard of care labs drawn within 45 days prior to consent may be used for the purposes of determining eligibility
1. ANC \>/= 1500/uL
2. platelets \>/=100,000/uL
3. Hemoglobin \>/= 9.0 g/dL
Exclusion Criteria:
1. Uveal or mucosal melanoma
2. Any women known to be pregnant or breastfeeding
3. Any prior systemic therapy for metastatic melanoma (prior surgery is allowed)
4. Known diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or equivalent), or any other form of immunosuppressive therapy within 7 days prior to first research biopsy
5. Patients with symptomatic CNS metastases and/or carcinomatous meningitis
a) Patients with asymptomatic, stable CNS metastases are allowed provided that they are not on \>10mg prednisone daily
6. History of or active (non-infectious) pneumonitis that required steroids
7. Active infection requiring systemic therapy
8. Known history of Human Immunodeficiency Virus (HIV) infection
9. Known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. NOTE: no testing for Hepatitis B or Hepatitis C is required
10. Known history of active TB (Bacillus Tuberculosis)
11. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or make it not in the best interest of the subject to participate, in the opinion of the treating physician
12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
13. History of allogenic tissue or solid organ transplant
14. History of allergic reaction to IPOL or Td vaccine
15. Receipt of Td vaccine within 30 days prior to starting IO therapy
A Feasibility Study of Mass-Based Response Drug Screening to Guide Personalized Hyperthermic Intraperitoneal Chemotherapy for High-Grade Appendiceal and Colorectal Adenocarcinoma With Peritoneal Metastasis
This trial uses a mass-based response testing (MRT) drug-screening device on patient tumor cells to select and deliver personalized hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases from high-grade appendiceal or colorectal adenocarcinoma.
NCT07291180 · Phase N/A · Yale University
Recruiting sites: Connecticut
Read full eligibility criteria
Inclusion Criteria:
* Has histologically confirmed peritoneal metastases with primary diagnosis of AJCC 8th Edition Stage IV
1. Appendiceal adenocarcinoma (moderately/poorly differentiated, and/or signet ring cell tumors)
2. Colorectal adenocarcinoma
3. Suspected colon, small bowel, or appendiceal adenocarcinoma in setting of unknown primary
* Limited or no extraperitoneal metastases (any of the below)
a) Any extraperitoneal metastases must be limited, stable and treatable
* Has adequate organ function, as described below; all screening laboratory tests should be performed within 30 days prior to the first HIPEC
* Expected survival at the time of first HIPEC is greater than 3 months
* Exhibits unresectable disease (bowel or mesenteric involvement) or PCI \> 19
Demographics
* Adult patient at least 18 years of age at the time of signing informed consent and less than 81 years of age at the time of signing informed consent.
* Has an ECOG performance status score of 0-2.
Male Participants
* A male participant must agree to use contraception (barrier birth control, abstinence) during the treatment period and for at least 95 days following completion, corresponding to time needed to eliminate any study intervention(s), and refrain from donating sperm during this period.
Female Participants
* A female participant of childbearing age is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception (hormonal, barrier birth control, or abstinence). Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.
Informed Consent
* The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR.
Alternative Eligibility
* In addition to the criteria above, if a patient has undergone less than 8 rounds of chemotherapy at another institution (prior to initial diagnostic laparoscopy) and has not undergone radiation, ablative procedures, or cytoreductive surgery, then they are still eligible to enter the study at the second diagnostic laparoscopy step
Exclusion Criteria:
* Has a positive urine pregnancy test within 3 days prior to randomization or treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Has a known allergy to medications used in this study. Note: In the event that 3 days have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study medication.
* Has hypoxia as defined by pulse oximeter reading \<92% at rest or requires intermittent or chronic supplemental oxygen.
* No concurrent malignancy that may interfere with the study aims at the discretion of the investigator.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has known significant extraperitoneal metastasis.
* Has creatine clearance \<60 mL/m\^2 per the Cockcroft-Gault formula
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from treatment initiation, or New York Heart Association Class III or IV congestive heart failure. Medially controlled arrhythmia stable on medication is permitted.
* Has poorly controlled hypertension defined as SBP ≥150mmHg and/or DBP ≥90mmHg.
* Has moderate to severe hepatic impairment (Child-Pugh B or C).
* Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
* Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (severe dysphasia, bowel obstruction, malabsorption).
* Has progressive disease following the first 3 months of systemic chemotherapy prior to HIPEC who is not in a stable condition to continue with the trial.
Prior/Concomitant Therapy
* Has received radiation, ablative procedures, cytoreductive surgery, or systemic therapy including chemotherapy to treat metastatic disease within 3 months of initial laparoscopy.
Diagnostic Assessments
* Has an active infection requiring systemic therapy.
* Has a known active TB/ COVID infection.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention.
* Has a known history of poorly controlled HIV infection despite anti-retroviral therapy.
* Has a known history of HBV (defined as HBsAg reactive) or known active HCV (defined as HCV RNA \[qualitative\] is detected) infection that is poorly controlled.
Note: Testing for HBV and HCV is only required if mandated by the local health authority.
Other Exclusions
* Inability to receive chemotherapy due to medical/insurance reasons.
* Requires emergency surgery due to bleeding, perforation, or obstruction.
* Has undergone previous iterative intraperitoneal therapy.
* Has contraindication to chemotherapy of choice.
A First in Human Study of ALX2004 With Advanced or Metastatic Selected Solid Tumors
ALX2004, an antibody-drug conjugate targeting EGFR conjugated to a topoisomerase I inhibitor, is being studied as a first-in-human treatment in patients with advanced or metastatic HNSCC, NSCLC, esophageal squamous cell carcinoma, or colorectal cancer who have progressed on prior therapy.
NCT07085091 · Phase 1 · ALX Oncology Inc.
Recruiting sites: California, Florida, Michigan, New Jersey, Ohio, Oregon, Texas, Utah, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
* Participants with locally advanced, recurrent or metastatic histologically confirmed HNSCC, NSCLC, ESCC, CRC; locally advanced or recurrent disease must not be amenable to resection with curative intent
1. Dose Escalation: Participants who have relapsed or progressed following prior anticancer therapy in the advanced/metastatic setting and for whom no approved or standard therapy is available.
2. Dose Exploration and Dose Expansion: The following tumor-specific criteria also apply. These cohorts will include all or a subset of these tumors.
HNSCC - Received no more than 3 prior lines of therapy in the advanced or metastatic setting
NSCLC - For participants with a targetable molecular alteration: received appropriate standard targeted therapy and no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting. For participants without a targetable molecular alteration: received platinum-based chemotherapy and CPI (in combination or separately), and have received no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting
ESCC - Received no more than 3 prior lines of therapy in the advanced/metastatic setting
CRC - For participants with a targetable molecular alteration (including dMMR or MSI-H): Received appropriate standard therapy for the alteration, at least 2 prior lines of systemic chemotherapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting. For participants without a targetable molecule alteration: Received at least 2 prior lines of systemic chemotherapy (including an oxaliplatin-based chemotherapy), vascular endothelial growth factor (VEGF)-based therapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting.
* Adequate Bone Marrow Function
* Adequate Renal \& Liver Function
* Adequate Performance Status
Exclusion Criteria:
* Participants with disease suitable for local therapy with curative intent.
* Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator
* Prior treatment with any ADCs that have an active TOP1 inhibitor-based component
A First in Human Study of PLT012 in Participants With Solid Tumor Cancers
PLT012 is an anti-CD36 monoclonal antibody being tested in a first-in-human dose-escalation study for adults with advanced/metastatic solid tumors, including hepatocellular carcinoma with specific eligibility provisions.
NCT07337525 · Phase 1 · Pilatus Biosciences Inc
Recruiting sites: California, Texas
Read full eligibility criteria
Inclusion Criteria:
* Aged at least 18 years and provided written informed consent
* Histologically or cytologically confirmed advanced solid tumors (except primary CNS malignancies)
* Has at least one measurable lesion per RECIST v1.1
* ECOG PS of 0 to 1
* Life expectancy of ≥ 12 weeks
* Child-Pugh score of Class A (for hepatocellular carcinoma only)
* Adequate organ function as defined by protocol-specified laboratory values
* Not pregnant or breastfeeding
Exclusion Criteria:
* Insufficient washout period from prior therapies as defined in the study protocol
* Ongoing Grade 2 or higher toxicities from prior treatments (with some exceptions)
* Concurrent or recent (within 2 years) malignancy other than the disease under study (with some exceptions)
* Uncontrolled HIV, uncontrolled hepatitis B, or uncontrolled acute hepatitis C infections
* Unstable/uncontrolled or untreated central nervous system (CNS) metastasis
* Active or recent (within 3 years) autoimmune disease requiring medical treatment
* Recipient of any organ transplant including allogeneic stem-cell transplant
* Clinically significant and active cardiovascular disease
* Known active alcohol or drug abuse
* Psychiatric disorders that would prohibit the understanding of the Informed Consent Form
* Ascites requiring therapeutic paracentesis or hepatic encephalopathy requiring medical interventions within the past 6 months (if hepatocellular carcinoma)
A First-In Human (FIH) Study to Find Out How Well REGN10597 Medicine Given Alone or in Combination With Cemiplimab Works in Adult Participants Who Have Cancer With Tumors That Have Spread in Their Body
REGN10597, a PD-1-targeted antibody fused to a masked IL-2 cytokine, is being studied alone or with the PD-1 inhibitor cemiplimab in patients with advanced/metastatic solid tumors including melanoma and clear-cell renal-cell carcinoma, in both anti-PD-(L)1-progressed and first-line settings.
NCT06413680 · Phase 1/2 · Regeneron Pharmaceuticals
Recruiting sites: California, Connecticut, Illinois, Michigan, New York, North Carolina, Pennsylvania, Texas
Read full eligibility criteria
Key Inclusion Criteria:
Dose escalation cohorts:
1\. Histologically or cytologically confirmed diagnosis of solid malignancy (locally advanced or metastatic) with confirmed progression on standard-of-care therapy. Participants are required to submit archival tissue if it is available
Dose expansion cohorts:
1\. Histologically of cytologically confirmed diagnosis of one of the following tumors with criteria, as defined in the protocol:
* Module 1, Cohort 1: anti-PD-(L)1 Progressed Melanoma or
* Module 1, Cohort 2: anti-PD-(L)1 Progressed RCC or
* Module 2, Cohort 1: 1L Melanoma ALL Participants ARE REQUIRED to submit fresh pretreatment biopsy during screening, with an additional exploratory biopsy at other time points
Key Exclusion Criteria:
1. Prior treatment with Interleukin 2 (IL2)/IL15/IL-7 given outside the context of concurrent administration with adoptive cell therapy
2. Prior treatment with anti-PD1/PD-L1, or an approved systemic therapy or any previous systemic non-immunomodulatory biologic therapy within 4 weeks, as defined in the protocol
3. Has received radiation therapy or major surgery within 14 days prior to first dose of study drug or has not yet recovered from AEs
4. Has had prior anti-cancer immunotherapy within 4 weeks prior to study intervention, or discontinuation of prior anti-cancer immunotherapy due to grade 3 or 4 toxicities
5. Has ongoing immune-related AEs prior to initiation of study intervention, as defined in the protocol
6. Has known allergy or hypersensitivity to components of the study drug(s)
7. Has any condition requiring ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1-2 weeks to the first dose of study intervention
8. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments
NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply.
A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors
VVD-130037, an oral agent whose mechanism is not stated in the registry, is being studied as monotherapy and in combination with docetaxel, paclitaxel, or pembrolizumab in a first-in-human dose escalation/expansion trial for advanced solid tumors including esophageal squamous cell carcinoma refractory to prior therapy.
NCT05954312 · Phase 1 · Vividion Therapeutics, Inc.
Recruiting sites: Florida, Minnesota, Tennessee, Texas, Virginia
Read full eligibility criteria
Key Inclusion Criteria for Parts 1 and 2:
* Histologically or cytologically confirmed metastatic or unresectable solid tumor.
* Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the Investigator.
* Have progressed on or after all prior standard-of-care therapies for metastatic disease.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
* Adequate organ and marrow function as defined in the protocol.
Additional Key Inclusion Criteria for Part 2:
* Participants with squamous non-small cell lung cancer (sqNSCLC) with or without nuclear factor erythroid 2-related factor 2 (NRF2 \[NFE2L2\]) and/or cullin 3 (CUL3) mutations.
* Participants with advanced sqNSCLC must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor.
* Participants with advanced head and neck squamous cell carcinoma (HNSCC) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known programmed death-ligand 1 \[PD-L1\] expression, microsatellite instability-high, or mismatch repair deficiency, and an anti-epidermal growth factor receptor agent) (Combination Expansion Cohort).
* Participants with advanced esophageal squamous cell carcinoma (ESCC) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known PD-L1 expression) (Combination Expansion Cohort).
* Participants with a known driver mutation, including activating epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, should have progressed after appropriate targeted treatment.
* Participants with known human epidermal growth factor receptor 2 overexpression should have progressed after appropriate targeted treatment.
Key Exclusion Criteria for Parts 1 and 2:
* Participant is known to have a mutation that has no expectation of benefit from VVD-130037. Current such mutations include the following:
1. KEAP1 nonsense mutation (any position)
2. KEAP1 frameshift mutation (any position)
* Any unresolved toxicity Grade ≥2 per CTCAE version 5.0 from previous anticancer treatment.
* Current or prior treatment with anti-epileptic medications for the treatment or prophylaxis of seizures.
* History of seizure or condition that may predispose to seizure.
* History or presence of central nervous system (CNS) metastases or spinal cord compression.
* Uncontrolled arterial hypertension despite optimal medical management.
* Risk factors for abnormal heart rhythm/QT prolongation as defined in the protocol.
* History of the following cardiac diseases:
i) congestive heart failure (New York Heart Association \[NYHA\] Class \>II), ii) unstable angina, iii) new onset angina within past 6 months, iv) myocardial Infarction within the past 6 months, v) clinically significant arrhythmias within past 6 months.
* Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation (Combination Expansion Cohort)
* Medical history of (noninfectious) pneumonitis/interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active pneumonitis/ILD (Combination Expansion Cohort)
A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors, Carcinomas and Malignant Peripheral Nerve Sheath Tumors
ADCT-701, an anti-DLK-1 antibody-drug conjugate carrying a pyrrolobenzodiazepine dimer payload, is being tested in a first-in-human phase I trial for patients with advanced/metastatic neuroendocrine neoplasms, adrenocortical carcinoma, or malignant peripheral nerve sheath tumors who are refractory to standard therapy.
NCT06041516 · Phase 1 · National Cancer Institute (NCI)
Recruiting sites: Maryland
Read full eligibility criteria
* INCLUSION CRITERIA:
* Participants must have histologically or cytologically confirmed neuroendocrine neoplasms or malignant adrenocortical carcinoma (ACC) or malignant peripheral nerve sheath tumors (MPNST).
* Locally advanced, unresectable or metastatic disease (as confirmed by a radiological evaluation)
* Participants must have measurable disease per RECIST 1.1.
* Participants must have received prior standard of care treatment and be refractory to or intolerant to standard of care therapy(s). Note: Patients with MPNST who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic
chemotherapy is felt to be in the best interest for the patient by the local investigator and treating investigator will also be eligible.
* Age \>= 18 years.
* ECOG performance status \<= 2.
* Adequate hematologic function as follows:
* Leukocytes \>= 3,000/microliter
* Absolute neutrophil count (ANC) \>= 1,200/microliter (off-growth factors for 72 hours prior to treatment initiation)
* Hemoglobin (Hgb) \>= 9 g/dL with no blood transfusion within 2 weeks prior to treatment initiation
* Platelets \>= 100,000/microliter with no platelet transfusion within 1 week.
* Adequate renal and hepatic function as follows:
* Creatinine clearance (CrCl) \>= 50 mL/min/1.73 m\^2 (calculated CrCl (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or calculated eGFR provided by a laboratory))
* Total bilirubin \<= 1.5 x ULN OR in participants with known or suspected Gilbert's syndrome, total bilirubin \<= 3.0 x ULN
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 2.5 x ULN, (unless liver metastases are present, then values must be \<= 5 x ULN).
* Participants serologically positive for hepatitis C virus (HCV) must have an undetectable HCV viral load.
* Participants serologically positive for Hepatitis B (HBV) core antibody or surface antigen must be on adequate anti-viral therapy and Hepatitis B Viral deoxyribonucleic acid (DNA) load must be \<2000 IU/mL.
* Participants serologically positive for human immunodeficiency virus (HIV) must be on stable antiretroviral therapy for at least 4 weeks before treatment initiation, have no reported opportunistic infections or Castleman s disease within 12 months prior to treatment initiation, have a viral load that is undetectable by quantitative polymerase chain reaction (PCR) and CD4 count \>= 200 cells per cubic millimeter.
* Participants with brain metastasis are eligible if at least 4 weeks status post radiotherapy or surgery before treatment initiation with no evidence of progression or associated symptoms.
* Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 9.5 months after the last dose of the ADCT-701 (restriction period).
Individuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 6.5 months after the last dose of the ADCT-701.
* Nursing participants must be willing to discontinue nursing from study treatment initiation through 6.5 months after study treatment discontinuation.
* Participants or legally authorized representative (LAR) must be able to understand and be willing to sign a written informed consent document.
EXCLUSION CRITERIA:
* Major surgery, prior treatment with chemotherapy, hormonal therapy, immunotherapy, treatment with an investigational agent, and/or radiation therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to treatment initiation.
* Participants taking any herbal supplements within 14 days prior to treatment initiation.
* Participants who have wound dehiscence from prior surgeries.
* Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or any serosal effusion that is either requires drainage or is associated with shortness of breath) at screening.
* Active infection requiring systemic antibiotic therapy at screening.
* Active bleeding diathesis or therapeutic anticoagulation with an oral vitamin K antagonist with target international normalized ratio (INR) \> 2 at screening.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug.
* An active autoimmune disease. Note: Participants with type 1 diabetes, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease, adrenal insufficiency on systemic oral corticosteroid therapy (\<= the equivalent of prednisone 10 mg/day), or other mild autoimmune disorders (Type 1 diabetes, eczema, vitiligo, alopecia, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, adrenal insufficiency due to Addison's disease, hypothyroidisms due to Hashimoto's thyroiditis, hyperthyroidisms due to Graves disease, Sjogren s syndrome, celiac disease, pernicious anemia) not requiring immunosuppressive treatment are eligible.
* Congenital long QT syndrome, or a corrected QTcF interval of \>=480 ms, at screening (unless secondary to the pacemaker or bundle branch block).
* Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that does not require current anticancer treatment per standard of care.
* Live vaccine administration within 30 days prior to treatment initiation.
* Pregnant individuals (confirmed by Beta-Human Chorionic Gonadotropin \[Beta-HCG\] serum or urine pregnancy test) performed at screening.
* Uncontrolled intercurrent illness that would limit compliance with study requirements.
A First-in-Human Study of BMS-986506 in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
This is a first-in-human phase 1 study of BMS-986506, given alone or in combination with Pumitamig and/or Ipilimumab (mechanisms of BMS-986506 and Pumitamig not stated in the registry), in patients with locally advanced or metastatic clear cell renal cell carcinoma who have had prior systemic therapy or, in one cohort, no prior systemic therapy for metastatic disease.
NCT07195682 · Phase 1 · Bristol-Myers Squibb
Recruiting sites: Massachusetts, New York, Pennsylvania, Tennessee, Texas
Read full eligibility criteria
Inclusion Criteria
* Participants must have histologically confirmed diagnosis of locally advanced or metastatic ccRCC.
* For part 1: Participants must have already had at least two different treatment plans in the past, including immunotherapy and a targeted therapy.
* For part 2: Participants must have had at least one standard treatment plan that included both a PD-1/L1 inhibitor and a VEGF-TKI (either together or one after the other).
* Part 3: Participants must have had at least 1 standard treatment regimen (including a PD-1/L1 checkpoint inhibitor and/or a VEGF-TKI).
* Part 4: Participants must not have received prior systemic therapy for metastatic RCC, but may have received prior adjuvant therapy for completely resected RCC with PD-1 inhibitor if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.
* Eastern Cooperative Oncology Group performance status of 0 to 1.
Exclusion Criteria
* Inability to administer and/or tolerate oral medication without chewing, breaking, crushing, or otherwise altering the product dosage form.
* Part 2A: Participants who have received more than 3 prior systemic regimens for locally advanced or metastatic ccRCC including prior treatment with HIF2a inhibitors.
* Part 2A and Part 4: Participants who have received prior treatment with belzutifan (or another HIF2a inhibitor).
* Part 3B and Part 4B: Participants who have received prior ipilimumab (or another anti-CTLA-4 containing antibody).
* Participants who have hypoxia as defined by a pulse oximeter reading \< 92% at rest or requires intermittent or chronic supplemental oxygen.
* Participants who have received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) within 28 days prior to the first dose of study intervention.
* Part 3 and Part 4: Participants with a history of Grade ≥3 immune-mediated AEs leading to discontinuation of prior immunotherapy.
* Other protocol-defined Inclusion/Exclusion criteria apply.
A First-in-Human Study of CKD-703 in Advanced Solid Tumors and Non-Small Cell Lung Cancer
CKD-703, a c-Met-targeted antibody-drug conjugate delivering MMAE, is being studied in advanced c-Met expressing solid tumors and MET-amplified/c-Met overexpressing non-small cell lung cancer that failed prior standard therapy.
NCT07439094 · Phase 1/2 · Chong Kun Dang Pharmaceutical
Recruiting sites: Ohio
Read full eligibility criteria
Inclusion Criteria:
* Males and females ≥ 19-year-old
* Part 1 : Solid tumors including NSCLC for which standard therapy has failed or was not tolerated, and no other effective therapy exists
* Part 2 : Histologically or cytologically documented c-Met overexpressing nonsquamous NSCLC having failed at least 1 line of SoC therapy (platinum-based chemotherapy and/or immune checkpoint inhibitor).
* Part 3 : Histologically or cytologically documented c-Met expressing solid tumors for which standard therapy has failed or was not tolerated.
* In all parts of the study, subjects with NSCLC with documented actionable genetic alterations must have failed at least 1 line of country-level approved targeted therapies
* Life expectancy ≥ 12 weeks as judged by the Investigator
* Documented progressive and measurable disease as defined by RECIST 1.1
* ECOG Performance Status 0 or 1
Exclusion Criteria:
* Subject has received radiation therapy to the lung \< 6 months prior to the first dose of study drug
* Prior radiotherapy to ≥ 25% of bone marrow
* Anticancer systemic therapy such as immunotherapy, biologic, cytotoxic chemotherapy, or any investigational therapy (including cell therapy or gene therapy) within a period of 28 days prior to the first dose of study drug. Any anticancer therapy small molecule (eg. kinase inhibitor) or herbal therapy within 14 days prior to the first dose of study drug
* Prior c-Met-targeted antibody therapy or any MMAE-containing ADC (prior c-Met targeting small molecules are allowed)
* Use of strong P-gp and/or CYP3A4/5 inducers within 21 days prior or strong P-gp and/or CYP3A4/5 inhibitors within 14 days prior to the first dose of study drug
* Use of sensitive CYP3A4/5 substrate within 3 days or 5 times half-life prior to the first dose of study drug.
* Evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis that required treatment with systemic steroids within 12 months of the planned first dose of the study drug
* History of drug induced interstitial lung disease
* Prior or active ocular or corneal disease based on ophthalmic evaluation (slit lamp and visual acuity)
* Prior Grade 3 neuropathy or chronic Grade 2 neuropathy
A First-in-Human Study of MEN2312 in Adults With Advanced Breast Cancer
MEN2312, an oral KAT6 (lysine acetyltransferase 6) inhibitor, is being studied alone or with elacestrant in a first-in-human trial for adults with advanced breast cancer previously treated with endocrine therapy and CDK4/6 inhibitors.
NCT06638307 · Phase 1 · Stemline Therapeutics, Inc.
Recruiting sites: Arkansas, California, Connecticut, Florida, Georgia, Illinois, Iowa, Kansas, Maryland, Massachusetts, Michigan, Minnesota, New Jersey, New York, Oregon, Tennessee, Texas, Utah, Virginia, Wisconsin
Read full eligibility criteria
Key Inclusion Criteria:
* Participant has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
* Presence of genetic alterations in PIK3CA/AKT1/PTEN in participants' tumor tissue.
* Participant must have received at least 1 prior line of endocrine therapy for advanced/metastatic disease or participant who has radiological evidence of breast cancer recurrence or progression during or within 12 months from the end of adjuvant treatment with endocrine therapy, as these participants are considered as first-line relapsed participants.
* Progression on previous cyclin-dependent kinase 4 and 6 inhibitor treatment in combination with fulvestrant or aromatase inhibitor is required.
Key Exclusion Criteria:
* Active or newly diagnosed central nervous system metastases.
* Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement \>50%.
* Participants with any toxicities related to prior radiation therapy that have not resolved to baseline or to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2).
Note: Other inclusion/exclusion criteria may apply.
A First-in-Human Study of MEN2501 in Participants With Platinum-Resistant Ovarian Cancer
MEN2501 is an oral drug whose mechanism of action is not stated in the registry, given as monotherapy in a first-in-human dose-escalation trial for platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.
NCT07226427 · Phase 1 · Stemline Therapeutics, Inc.
Recruiting sites: Arkansas, Connecticut, Florida, Massachusetts, Michigan, Minnesota, Virginia
Read full eligibility criteria
Key Inclusion Criteria:
* Participants must have a histopathologically confirmed diagnosis of high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
Key Exclusion Criteria:
* Participants with primary platinum-refractory disease.
Note: Other protocol-defined inclusion/exclusion criteria may apply.
A First-in-Human Study to Evaluate Implantable Iontophoresis Chemotherapy Delivery Device With Gemcitabine Once Weekly or Twice Weekly in Participants With Pancreatic Cancer
ACT-IOP-003 is an implantable iontophoresis device that delivers gemcitabine chemotherapy directly to the tumor site, studied in a first-in-human trial for nonmetastatic, locally advanced/unresectable pancreatic adenocarcinoma after prior standard-of-care chemotherapy.
NCT07481383 · Phase 1 · Continuity Biosciences, LLC
Recruiting sites: Michigan, West Virginia
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
* Diagnosis of nonmetastatic, nonresectable pancreatic adenocarcinoma as evident on initial study. screening computed tomography (CT) or magnetic resonance imaging (MRI) or previous scan within the last 12 weeks.
* Initial diagnosis of borderline or locally advanced pancreatic adenocarcinoma confirmed as being nonresectable at the time of exploratory laparoscopic and/ or open surgery.
* Previously received prior standard of care/neoadjuvant chemotherapy of FOLFIRINOX or GEM Abraxane for their current diagnosis of pancreatic cancer.
Exclusion Criteria:
* Current pancreatitis classified as severe or critical.
* Prior radiation treatment as part of standard of care/neoadjuvant treatment for pancreatic cancer.
* Evidence of metastatic pancreatic cancer or any other type of cancer upon screening of through CT/MRI.
* Any medical history of past or present cardiovascular disease related to heart function.
* Any metal implants.
Note: Other inclusion/exclusion criteria apply.
A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations
BLU-924 (SAR449336), an oral pan-KRAS inhibitor, is being studied as monotherapy in a first-in-human trial for patients with metastatic KRAS-mutant pancreatic ductal adenocarcinoma, non-small cell lung cancer, or colorectal cancer who have received all standard therapies.
NCT07629960 · Phase 1/2 · Blueprint Medicines Corporation
Recruiting sites: Florida, Louisiana, Massachusetts, Michigan, New Jersey, New York, Tennessee, Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Pathologically confirmed diagnosis of metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) with evidence of a single KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA).
2. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
4. Patients must have received all standard therapies for their cancer type in the metastatic setting, unless they are unable to receive such therapies due to clinical characteristics, comorbidities, or other medically justified reasons.
Exclusion Criteria:
1. History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol.
2. Active brain metastases (participants with asymptomatic brain metastases may be eligible).
3. Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders.
4. Active or uncontrolled systemic infection, such as tuberculosis, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
A First-in-human Study of RLY-8161 in Advanced NRAS-Mutant Solid Tumors
RLY-8161, an orally bioavailable NRAS-selective inhibitor, is being tested as a first-in-human treatment in patients with advanced NRAS-mutant melanoma and other NRAS-mutant solid tumors refractory to or intolerant of standard therapy.
NCT07584226 · Phase 1 · Relay Therapeutics, Inc.
Recruiting sites: California, Colorado, Massachusetts, Michigan, New York, Tennessee, Virginia
Read full eligibility criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Histologically confirmed diagnosis of unresectable Stage III or IV melanoma or other solid tumor.
* Disease is refractory to standard therapy (including targeted therapy), participant is intolerant of standard therapy, or participant has declined standard therapy.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* One or more documented primary oncogenic NRAS mutation(s).
Exclusion Criteria:
* Known activating KRAS, HRAS, or BRAF mutation or known alterations in other driver oncogenes.
* Prior treatment with ERK, MEK, RAF, or RAS targeting agents or any agent whose mechanism of action is to inhibit the RAS-MAPK pathway.
* For participants with melanoma: lactate dehydrogenase (LDH) \>2×ULN.
* Central nervous system (CNS) metastases that are associated with progressive neurologic symptoms or require ongoing corticosteroids to control the CNS disease.
A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer
BAY 3547926, a GPC3-targeted antibody conjugate carrying an actinium-225 radioisotope payload, is being studied as first-in-human treatment for advanced/unresectable hepatocellular carcinoma with confirmed GPC3 expression, given alone or with other treatments in later parts of the trial.
NCT06764316 · Phase 1 · Bayer
Recruiting sites: Alabama, California, Florida, Tennessee
Read full eligibility criteria
Inclusion Criteria:
* Locally advanced or metastatic and/or unresectable HCC (hepatocellular carcinoma) with histological or cytological confirmation, or non-invasive diagnosis as per American Association for the Study of Liver Diseases (AASLD) criteria in participants with a confirmed diagnosis of cirrhosis.
* Demonstrated positive centrally confirmed GPC3 expression by immunohistochemistry (IHC) on tumor sample.
* Disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies of established efficacy such as resection, local ablation, chemoembolization.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
* At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. as assessed by local site Investigator within 28 days prior to the start of the study treatment.
* Adequate bone marrow and organ function
Exclusion Criteria:
* Fibrolamellar HCC, sarcomatoid HCC, and mixed hepatocellular/cholangiocarcinoma subtypes.
* Participants with a history or clinical evidence of CNS metastases, unless they meet specific criteria
* History of encephalopathy ≥ Grade 2 within the past 12 months
* Clinically significant ascites
A First-in-human, Phase I, Open-label, Multicenter Study of NM1F(Anti-PVRIG) in Patients With Advanced Solid Tumors
NM1F, an anti-PVRIG monoclonal antibody immune checkpoint inhibitor, is being studied as monotherapy and combined with pembrolizumab in patients with unresectable locally advanced or metastatic solid tumors (including colorectal, triple-negative breast, melanoma, and ovarian cancers) who have failed or lack standard therapy.
NCT05746897 · Phase 1 · Hefei TG ImmunoPharma Co., Ltd.
Recruiting sites: Texas, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Male or female subjects age ≥ 18 years at the time of informed consent.
2. Subjects with histologically or cytologically diagnosed unresectable locally advanced, or metastatic solid tumors, mainly but not limited to CRC, TNBC, melanoma, OC, and who have progressed despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists
3. Subjects must have at least 1 evaluable lesion as defined by response evaluation criteria in solid tumors (RECIST) v1.1.
4. ECOG PS of 0\~2.
5. Life expectancy ≥ 3 months.
6. Subjects have sufficient baseline organ function and laboratory data.
7. Woman of childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment.
8. Female subjects of childbearing potential or male subjects with a partner of childbearing potential must agree to use effective contraception at the time of informed consent and continuing through the study until 6 months after the last dose of NM1F and / or pembrolizumab.
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Exclusion Criteria:
Cancer Related
1. Subject with known active central nervous system (CNS) primary tumor or metastases.
2. History of intercurrent severe chronic or active infections.
3. Has a history of active autoimmune diseases , or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study drug.
4. Has a history of symptomatic interstitial lung disease or inflammatory pneumonitis.
5. Has a history of impaired cardiac function or clinically significant cardiovascular diseases.
6. Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years (Note: Exceptions are subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and localized prostate cancer who have undergone potentially curative therapy. These subjects are not excluded).
8. Evidence of clinically significant immunosuppression such as the following:
1. Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease (SCID)
2. Concurrent opportunistic infection
9. Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (monthly or more frequently).
10. Has received prior anticancer treatment with the following therapies (specified time periods are from last dose of prior treatment to first dose of NM1F):
1. Any therapy directed against PVRIG (COM701 or other anti-PVRIG mAb) or other CD226 axis receptor (TIGIT or CD96) at any time.
2. Chemotherapy, target therapy, immunotherapy, or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
3. Prior radiotherapy ≤ 4 weeks prior to the first dose of study treatment, with the exception of a single fraction of radiotherapy for the purposes of palliation, which is permitted.
4. Investigational therapy: if the subject has participated in a clinical study and has received an investigational product within 4 weeks prior to the first dose of study treatment.
11. Has received systematic immunomodulatory drugs within 14 days before the first dose of study drug, such as thymosin, IL-2, IFN.
12. Has received a live vaccine within 4 weeks prior to the first dose of study drug.
13. Has a recent major surgery within 4 weeks prior to the first dose of study drug or is expected to undergo major surgery during the study.
14. Toxicities of prior therapies have not been resolved to ≤ Grade 1 or baseline as per NCI-CTCAE v5.0, except for alopecia, skin hyperpigmentation.
15. Subjects who have experienced Grade ≥ 3 irAEs from prior immunotherapies or who discontinue immunotherapy due to immune-related toxicities.
16. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
17. Pregnancy or lactation. Women who are willing to discontinue breastfeeding prior to administration of study drug and do not intend to resume breastfeeding may be enrolled.
18. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the investigator.
20. Subjects who are unwilling or unable to comply with study procedures and study restrictions, or in the judgment of the investigator, would make the subject inappropriate for entry into this study.
21. Subjects who have contraindication for use of PD-1/PD-L1 antibody (only for Phase 1b).
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A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer
This phase 3 trial compares rilvegostomig (a biologic, target/mechanism not specified in the registry) versus pembrolizumab as first-line monotherapy in PD-L1-high metastatic non-small cell lung cancer.
NCT06868277 · Phase 3 · AstraZeneca
Recruiting sites: California, Delaware, Florida, Georgia, Illinois, Iowa, Kansas, Kentucky, Maryland, Michigan, Missouri, Nebraska, Nevada, New Jersey, New York, Ohio, Pennsylvania, Texas, Washington, West Virginia, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically documented NSCLC (non small lung cancer), including all histological subtypes.
* Stage IV mNSCLC (metastatic non-small cell lung cancer) (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
* Absence of sensitizing EGFR (epidermal growth factor) mutations and ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) rearrangements. Negative assay result is required for all non-squamous histology subtypes.
* Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L (first line) therapies.
* WHO (World Health Organization)/ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization.
* Minimum life expectancy of 12 weeks.
* Provision of acceptable tumor sample for the central testing prior to randomization.
* At least one lesion not previously irradiated that qualifies as a RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1) TL (target lesion) at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT (computed tomography) or MRI (magnetic resonance imaging) and is suitable for accurate repeated measurements.
* Adequate organ and bone marrow function
Exclusion Criteria:
* As judged by the investigator, any severe or uncontrolled systemic diseases, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
* History of organ transplant.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
* Presence of small cell and neuroendocrine histology components.
* Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention.
* Active primary immunodeficiency/active infectious disease(s)
* Active tuberculosis infection
* Any prior systemic therapy received for advanced or mNSCLC (metastatic non-small cell lung cancer).
* Any prior exposure to an anti-TIGIT (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* Any prior treatment with an anti-PD-1 (programmed cell death protein 1) or anti-PD-L1 (anti-programmed death-ligand 1) agent.
A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Non-Squamous NSCLC
This trial compares rilvegostomig (an anti-TIGIT/PD-1 agent implied by exclusion criteria referencing immune-regulatory receptor targeting, though its precise mechanism is not explicitly stated) versus pembrolizumab, each combined with platinum-based doublet chemotherapy, as first-line treatment for PD-L1-expressing, locally advanced or metastatic non-squamous NSCLC.
NCT06627647 · Phase 3 · AstraZeneca
Recruiting sites: Alabama, Arizona, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Iowa, Kentucky, Louisiana, Maine, Maryland, Michigan, Minnesota, Missouri, Nebraska, New Jersey, New York, Ohio, Oregon, Pennsylvania, Rhode Island, South Dakota, Tennessee, Texas, Virginia, Washington, Wisconsin
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically documented non-squamous NSCLC.
* Stage III B/C or IV NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
* Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
* Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved and available targeted 1L therapies.
* Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC ≥ 1%.
* At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
* Adequate organ and bone marrow function
Exclusion Criteria:
* Presence of small cell and neuroendocrine histology components.
* Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
* Any prior systemic therapy received for NSCLC except in the neoadjuvant or adjuvant setting or definitive chemoradiotherapy with the intent to cure, provided that progression has occurred \> 12 months after the end of systemic therapy treatment.
* Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs.
* Active primary immunodeficiency/active infectious disease(s).
* Active tuberculosis infection.
A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)
Rilvegostomig, a bispecific PD-1/TIGIT-targeting antibody, is being studied in combination with platinum-based chemotherapy versus pembrolizumab plus chemotherapy as first-line treatment for PD-L1-expressing locally advanced or metastatic squamous NSCLC.
NCT06692738 · Phase 3 · AstraZeneca
Recruiting sites: Arizona, Arkansas, California, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Michigan, Minnesota, Missouri, Nebraska, New Jersey, New York, North Carolina, North Dakota, Ohio, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically documented squamous NSCLC.
* Stage III B/C or IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
* Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any actionable driver oncogenes for which there are locally approved and available targeted 1L therapies.
* Provision of acceptable tumor sample to confirm tumor PD-L1 expression TC ≥ 1%.
* At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
* Adequate organ and bone marrow function.
Exclusion Criteria:
* Presence of small cell and neuroendocrine histology components.
* Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
* Any prior systemic, non-curative therapy received for NSCLC.
* Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
* Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents or other immunosuppressive drugs.
* Active primary immunodeficiency/active infectious disease(s).
* Active tuberculosis infection.
A Global Study of Volrustomig (MEDI5752) for Participants With Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma Following Definitive Concurrent Chemoradiotherapy
Volrustomig, a bispecific PD-1/CTLA-4 immune checkpoint inhibitor monoclonal antibody, is being studied as maintenance therapy versus observation in unresected locally advanced head and neck squamous cell carcinoma following definitive concurrent chemoradiotherapy.
NCT06129864 · Phase 3 · AstraZeneca
Recruiting sites: Alabama, Arizona, Arkansas, California, Colorado, District of Columbia, Florida, Illinois, Iowa, Kansas, Kentucky, Louisiana, Maryland, Massachusetts, Michigan, Minnesota, Missouri, New Jersey, New Mexico, New York, North Carolina, Ohio, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Virginia, Washington
Read full eligibility criteria
Inclusion Criteria:
* Histologically or cytologically documented locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, oral cavity, or larynx with no evidence of metastatic disease (i.e. M0).
* Confirmed unresected Stage III, Stage IVA or IVB according to the eighth edition of the American Joint Committee on Cancer (AJCC) staging manual (tumor, node, metastasis (TNM) staging system).
* Participants will have completed definitive concurrent chemoradiotherapy (cCRT) with curative intent prior to randomization.
Exclusion Criteria:
* Histologically/cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including participants with squamous cell carcinoma of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland). Participants with \>1 primary tumors are not eligible for the study.
* Participants with any of the following:
1. LA-HNSCC that was resected before definitive cCRT
2. LA-HNSCC that was treated and is recurrent at the time of screening
* Participants who have received radiotherapy (RT) alone as definitive local therapy for LA-HNSCC.
A Long-term Treatment Extension Study of Niraparib in Participants Who Completed a Prior GlaxoSmithKline/TESARO-sponsored Niraparib Study
Niraparib, an oral PARP1/2 inhibitor, is continued as long-term extension treatment for ovarian or breast cancer patients who were already benefiting from niraparib in prior GSK/TESARO-sponsored trials.
NCT04641247 · Phase 2 · GlaxoSmithKline
Recruiting sites: Arizona, California, Florida, Georgia, Illinois, Massachusetts, Michigan, New Jersey, New York, North Carolina, Ohio
Read full eligibility criteria
Inclusion Criteria:
* Participant is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
* Participant is willing and able to comply with scheduled visits, treatment plans, and any other study procedures.
* Participant is currently receiving treatment with niraparib (as monotherapy or in combination) in a GlaxoSmithKline/TESARO-sponsored study that has fulfilled the requirements for the primary objective.
* Participant is currently benefiting from treatment with niraparib as assessed by the Investigator according to the parent study protocol requirements.
* Participants of childbearing potential who are sexually active and their partners must agree to the use of an effective form of contraception throughout their participation during study treatment through 180 days after last dose of study drug.
Exclusion Criteria:
* Participant has been permanently discontinued from niraparib treatment in the parent study for any reason.
* Participant currently has unresolved toxicities for which niraparib dosing has been interrupted in the parent study. Participants meeting all other eligibility criteria may be enrolled once toxicities have resolved to allow niraparib treatment to resume.
* Participant is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug. Participant is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use during niraparib treatment and for 30 days after receiving the final dose of study treatment).
A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations
This phase 1b/2 trial tests the combination of adagrasib (a KRAS G12C inhibitor), cetuximab (an anti-EGFR antibody), and cemiplimab (an anti-PD-1 antibody) in previously treated metastatic microsatellite-stable colorectal cancer harboring KRAS G12C mutations.
NCT06412198 · Phase 1/2 · M.D. Anderson Cancer Center
Recruiting sites: Massachusetts, Texas
Read full eligibility criteria
Inclusion Criteria:
* Histologically confirmed diagnosis of advanced/metastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy
* Confirmed KRASG12C mutation status. If a molecular profiling report is not available, a representative paraffin-embedded tumor block or a minimum of 10 unstained slides will be requested for retrospective KRASG12C mutation testing.
* Unresectable or metastatic disease.
* Participants must have received at least one prior line of chemotherapy for metastatic disease with progression on treatment or intolerance to therapy.
* Presence of measurable disease per RECIST 1.1
* Willingness to participate in on-study related procedures, including mandatory biopsies (one baseline and one on-treatment biopsy).
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of the proposed combination in patients \<18 years of age, children are excluded from this study.
* Able to take oral medications.
* Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or investigational agent) and radiation therapy discontinued at least 7 days before first dose.
* Recovery from the treatment-related adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and prior oxaliplatin-induced neuropathy).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Laboratory values within the screening period:
* Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L)
* Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
* Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks
* Total bilirubin ≤ 1.5x upper limit of normal (ULN) (if associated with Gilbert's disease or UGT1A1\*28 homozygosity, ≤ 3x ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0x ULN (if associated with liver metastases ≤5x ULN)
* Calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 60mL/min at screening
* Completed informed consent process, including signing of IRB-approved informed consent form.
* Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
* Participants who are biologically capable of having children and sexually active must agree to use an acceptable method of contraception for the duration of the treatment period and for at least 6 months after the last dose of study treatment. The Investigator will counsel the patient on selection of contraception method and instruct the participant in its consistent and correct use. Examples of acceptable forms of contraception include:
* Oral, inserted, injected or implanted hormonal methods of contraception, provided it has been used for an adequate period of time to ensure effectiveness.
* Correctly placed copper containing intrauterine device (IUD).
* Male condom or female condom used WITH a spermicide.
* Male sterilization with confirmed absence of sperm in the post-vasectomy ejaculate.
* Bilateral tubal ligation or bilateral salpingectomy.
* The Investigator will instruct the participant to call immediately if the selected birth control method is discontinued or if pregnancy is known or suspected.
* Note: Women are considered post-menopausal and/or not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 months ago. In case of any ambiguity, the reproductive status of the woman should be confirmed by hormone level assessment.
Exclusion Criteria:
* Prior PD1 or CTLA4 inhibition therapy
* Prior KRASG12C inhibition therapy
* Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Active brain metastases, unless adequately treated and participant is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
* Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment within 10 days prior to study entry: known risk of QTc prolongation or Torsades de Pointes; substrate of CYP3A with a narrow therapeutic index; strong inducer or inhibitor of CYP3A and/or P-gp; strong inhibitor of BCRP; strong inhibitor or inducer of CYP2C19; and proton pump inhibitors.
Note: one dose of propofol, midazolam, and/or fentanyl under a monitored setting during IR guided biopsies is allowed.
* Pregnancy. Women of child-bearing potential must have a negative serum or urine pregnancy test during screening
* Breast-feeding or planning to breast feed during the study or within 6 months after end of treatment.
* Participants with symptomatic leptomeningeal disease.
* Major surgery within 4 weeks of first dose of any study drug.
* History of intestinal disease or major gastric surgery likely to alter absorption of study treatment, to be determined by the treating physician
* Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B (HBV) or C (HCV) infection as tested in a CLIA certified lab using a positive HIV antibody test. For Hepatitis B and C, an antigen that is drawn and positive. Note that the following are permitted:
* Participants treated for HIV with no detectable viral load on current regimen for at least 1 month prior to randomization;
* Note: Please refer to exclusion criteria regarding drug-drug interactions of concomitant anti-HIV agents, and in particular CYP3A substrates.
* Participants with prior HBV infections who are:
* considered to have past or resolved HBV infection, defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of hepatitis B surface antigen \[HBsAg\]; or
* considered to be in an inactive HBV carrier state, defined as HBsAg-positive with normal ALT, and HBV DNA \< 2,000 IU/mL or \< 10,000 copies/mL;
* Note: For participants in an inactive HBV carrier state or with a resolved HBV infection, the risk of HBV reactivation should be considered and the need for anti-HBV prophylaxis prior to randomization should be carefully assessed in accordance with local guidelines.
* Participants treated for HCV with no detectable viral load.
* Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the investigator's opinion, would be likely to interfere with the participant's participation in the study, or with the interpretation of results.
A Multinational Study Assessing an Oral EGFR Inhibitor, DZD6008 in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN1)
DZD6008 is an oral, mutant-specific, brain-penetrant EGFR inhibitor being studied in patients with advanced/metastatic EGFR-mutant NSCLC who have progressed on or are naive to prior EGFR TKI therapy.
NCT06905197 · Phase 1 · Dizal Pharmaceuticals
Recruiting sites: New York, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Patients must be able to provide documented informed consent.
2. Aged ≥ 18 years.
3. Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced or metastatic, not suitable for curative therapy.
4. Documentation of EGFR mutations from a local CLIA-certified laboratory (or equivalent). For Part A monotherapy cohorts and all cohorts of Part B, EGFR sensitizing mutations (Exon19del and/or L858R) are required.
5. Provide adequate amount of pretreatment tumor samples collected after disease progression on the last EGFR TKI treatment. (previously treated patients) or before study treatment (treatment naïve patients).
6. Part A: Failed (progressed or are intolerant) from at least 1 prior EGFR TKI regimen. Cohort A of Part B: Failed 1 prior third-generation EGFR TKI regimen. Cohorts B of Part B: Patients who are treatment naïve.
7. ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks.
8. Patients with brain metastases must have a stable BM status.
9. Measurable disease per RECIST 1.1.
10. Adequate hematopoietic and other organ system functions.
11. Male Patients with female partners of childbearing potential should use barrier contraceptives and refrain from donating sperm during their participation in this study and for 3 months following the last dose of the study drug.
Exclusion Criteria:
1. Carry other EGFR alterations than T790M and C797X, including but not limited to uncommon EGFR mutations (G719X, S768I, L861Q, exon 20 insertions mutations, etc.)(Part B).
2. NSCLC with mixed small cell lung cancer (SCLC) or NSCLC with histologic SCLC transformation.
3. Prior treatment with any of the following: 1)Immunotherapy or other antibody therapy within 4 weeks prior to the first administration; 2)Any cytotoxic chemotherapy, investigational drugs or other anticancer drugs from a previous treatment regimen or clinical study within 14 days prior to the first administration; 3)Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose, radiation to more than 30% of the bone marrow or with a wide field of radiation within 28 days before screening; 4)Currently receiving or unable to stop drug or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP)3A4. A washout period of at least 2 weeks for strong inhibitors and 3 weeks for strong inducers is required prior to the first study drug administration; 5)currently receiving or unable to stop drugs known to be CYP3A4 sensitive substrate with a narrow therapeutic index. A washout period of at least 14 days is required prior to the first study drug administration; 6)currently receiving or unable to stop drugs known to be proton pump inhibitors. A washout period of at least 7 days is required prior to the first study drug administration; 7)major surgery within 4 weeks of the first administration of DZD6008 or anticipated during the study period.
4. Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade 1.
5. Spinal cord compression or leptomeningeal metastasis.
6. Patients with any other malignancy within 2 years of the first administration of study drug.
7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses as judged by investigator.
8. Patients with active infection, including but not limited to HBV, HCV, HIV and active infection of COVID-19.
9. Resting QTcF \> 470 msec; Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG;Any factors that increase the risk of QTc prolongation.
10. Past medical history of ILD or active ILD.
11. Diseases which would preclude adequate absorption of DZD6008.
12. Received a live vaccine within 2 weeks before the first administration of DZD6008.
13. Women who are pregnant or breastfeeding.
14. Hypersensitivity to active or inactive excipients of DZD6008 or sunvozertinib.
15. Involvement in the planning and conduct of the study.
16. Judgment by the investigator that the patient is unlikely to comply with study procedures
A Ph Ib Study of REGN5678 Plus Cemiplimab in Patients With mCRPC
Phase Ib study of REGN5678 (mechanism not stated in registry) combined with cemiplimab (an immune checkpoint inhibitor) administered by IV in patients with metastatic castration-resistant prostate cancer who have progressed after at least two prior lines of systemic therapy.
NCT06826768 · Phase 1 · M.D. Anderson Cancer Center
Recruiting sites: Texas
Read full eligibility criteria
Inclusion Criteria:
1. Men .18 years of age.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
3. mCRPC with disease progression after at least two lines of systemic therapy, including one line of second-generation anti-androgen therapy, according to one of the following criteria:
1. PSA progression as defined by a rising PSA level confirmed with an interval of \>1 week between each assessment.
2. Radiographic disease progression in soft tissue based on RECIST Version 1.1 criteria with PCWG3 modifications with or without PSA progression.
3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.
NOTE: Prior approved PSMA-targeted therapies \[e.g. 177Lu-PSMA-617\] and immunotherapy (including sipuleucel-T and immune checkpoint therapies) are permitted.
4. Have had either orchiectomy OR be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with serum testosterone \<50 ng/dL AND agree to stay on LHRH agonist or antagonist therapy during the study.
5. ECOG performance status (PS) grade of 0 or 1.
6. Adequate organ and bone marrow function documented by:
1. Hemoglobin .8.5 g/dL
2. Absolute neutrophil count .1.0 x 109/L
3. Platelet count .100 x 109/L
7. Serum creatinine .1.5 x ULN or estimated glomerular filtration rate \>50 mL/min/1.73 m2.
8. Adequate hepatic function:
1. Total bilirubin .1.5 x ULN
2. AST .2.5 x ULN
3. ALT .2.5 x ULN
4. Alkaline Phosphatase (ALP) .2.5 x ULN (.5 x ULN if tumor liver or bone involvement).
NOTES: Patients with Gilbert fs syndrome do not need to meet total bilirubin requirements provided their total bilirubin is not greater than their historical level. Gilbert fs syndrome must be documented appropriately as past medical history.
9. Consent to MD Anderson laboratory protocols PA13-0291 and Lab02-152.
10. Willing and able to comply with clinic visits and study-related procedures including provision of tumor tissue.
11. Provide informed consent signed by study patient.
12. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 6 months following the last dose of study drug. If the subject is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies and their partners. Donation of sperm is not allowed while on study drug and for 6 months following the last dose of study drug.
Exclusion Criteria:
1. Currently receiving treatment in another interventional study
2. Has participated in a study of an investigational drug within 4-weeks of first dose of study therapy.
3. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade .1 or baseline) from any acute toxicities except for laboratory changes as described in inclusion criteria or patients with grade 2\< neuropathy.
4. Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered (ie, grade .1 or baseline) from AEs, except for laboratory changes as described in inclusion criteria or patients with grade .2 neuropathy.
5. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy.
NOTE: Prior treatment with sipuleucel-T is permitted
6. Patients who have not recovered (ie, grade .1 or baseline) from immune-mediated AEs 3 months prior to initiation of study drug therapy except for endocrinopathies adequately managed with hormone replacement.
7. Another malignancy that is progressing or requires active treatment, except:
1. Non-melanoma skin cancer that has undergone potentially curative therapy
2. Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy)
8. Concurrent treatment with systemic corticosteroids (prednisone dose \>10 mg per day or equivalent) or other immunosuppressive drugs \<14 days prior to treatment initiation. Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted.
9. History of or known or suspected autoimmune disease (exception(s): subjects with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at screening are allowed).
10. Known evidence of an active infection requiring systemic therapy such as human immunodeficiency virus (HIV), active hepatitis, or fungal infection. Testing for hepatitis B and C infection will be performed at screening if not previously performed and documented.
11. History of clinically significant cardiovascular disease including, but not limited to:
* Myocardial infarction or unstable angina .6 months prior to treatment initiation
* Clinically significant cardiac arrhythmia
* Deep vein thrombosis, pulmonary embolism, stroke .6 months prior to treatment initiation
* Congestive heart failure (New York Heart Association class III-IV)
* Pericarditis/clinically significant pericardial effusion
* Myocarditis
12. Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) .2 years prior to enrollment.
13. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living \[ADLs\]) or uncontrolled seizures in the year prior to first dose of study therapy.
14. Known history of, or any evidence of interstitial lung disease, or active, non-infectious pneumonitis (past 5 years).
15. Receipt of a live vaccine within 4 weeks of planned start of study medication.
16. Prior allogeneic stem cell transplantation or recipients of organ transplants at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment.
17. Any medical, psychological or social condition that in the opinion of the investigator, would preclude participation in this study.
A Phase 0 Window of Opportunity Trial of Intratumoral Seasonal Influenza Immunization in Cutaneous Squamous Cell Carcinoma (CSCC) Patients Awaiting Curative Excision
Intratumoral injection of the inactivated seasonal influenza vaccine Fluzone is being studied as a pre-surgical (neoadjuvant window-of-opportunity) immunostimulatory treatment in patients with resectable, localized cutaneous squamous cell carcinoma awaiting Mohs excision.
NCT06664151 · Phase 1 · Dana-Farber Cancer Institute
Recruiting sites: Massachusetts
Read full eligibility criteria
Inclusion Criteria:
* Participants must have a diagnosis of cutaneous squamous cell carcinoma that has been biopsied and confirmed histologically. Mixed histology (such as basosquamous carcinoma, sarcomatous carcinoma) is allowed.
* Participants must have a skin tumor that measures 10 - 39 mm (not less than 10 mm and not more than 39 mm) in longest dimension by clinical exam. (Participants may have more than one untreated CSCC at the time of enrollment, but only one CSCC may be treated with the study agent.)
* Participants must be candidates for treatment (excision) by Mohs micrographic surgery.
* Age ≥18 years. Because CSCC is exceptionally rare in patients \<18 years of age, children are excluded from this study.
* ECOG performance status ≤3 (Karnofsky ≥40%, see Appendix A).
* Ability to understand and the willingness to sign a written informed consent document.
* For participants with a past medical history of Human immunodeficiency virus (HIV), they must be on effective anti-retroviral therapy with undetectable viral load measured within the 6 months prior to enrollment.
* For participants with a past medical history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* For participants with a past medical history of hepatitis C virus (HCV) infection, they must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Exclusion Criteria:
* CSCC with the following high-risk features including peri-neural invasion of \>0.1 mm caliber, and invasion of tissue beyond the subcutaneous fat, and a diameter \> 3.9 cm.
* Evidence of in-transit/satellite, nodal, or distant metastases from CSCC, in the present or in the past medical history, including evidence from physical exam of primary site and draining lymph node basin.
* History of solid organ transplant or allogeneic bone marrow transplant.
* History of allergic reactions attributed to the seasonal flu vaccine.
* History of Guillain-Barré syndrome.
* Participants with any uncontrolled intercurrent illness, including uncontrolled cardiac disease (New York Heart Association Class III or IV heart failure, myocardial infarction in the 6 months prior to enrollment, unstable angina).
* Participants who are receiving any other investigational agents for treatment of cancer.
* Participants with a past medical history of another malignancy whose natural history or treatment is likely to interfere with the safety or efficacy assessment of the investigational regimen, according to the treating investigator.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of intratumoral flu vaccine administration. Patients who do not agree to comply with these precautions are ineligible.
* Pregnant or nursing (breast-feeding) women are excluded from this study because there is an unknown but potential risk to multiple injections of flu vaccine in pregnant or nursing women.
* Note: Previous treatment with flu vaccination is not an exclusion criterion. Routine intramuscular seasonal influenza vaccination is not required nor prohibited.
A Phase 1 Dose Escalation Study of ZG006 in Patients With Small Cell Lung Cancer
ZG006 is a novel intravenous agent, whose specific mechanism is not stated but is being tested in DLL3-expressing small cell lung cancer patients who failed or are intolerant to standard treatment, in a phase 1 dose-escalation study.
NCT06592638 · Phase 1 · Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Recruiting sites: California, Florida, Kentucky, Ohio, Texas
Read full eligibility criteria
Inclusion Criteria:
* Small cell lung cancer (SCLC), who failed or intolerant to available standard treatments;
* Tissue sample positive for DLL3 expression;
* Life expectancy ≥ 3 months;
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
* Female and Male patients must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug.
Exclusion Criteria:
* Patients having received any of the following treatments:
* Chemotherapy, biotherapy, endocrine therapy (except for hormone replacement), and biological targeted medicines ≤ 4 weeks before the study entry. Local palliative radiotherapy and a small molecule targeted therapy ≤ 2 weeks (or 5 half-lives, whichever is longer) before the study entry;
* Systemic immunosuppressive medications, such as corticosteroid (doses \&gt; 10 mg/day prednisone or equivalent dose) within 14 days prior to the study entry;
* Use of any vaccines against viral infections (COVID-19, influenza, varicella, etc.) within 4 weeks of study entry;
* Patients received any blood transfusion, EPO, G-CSF, albumin infusion and renal replacement therapy within 14 days prior to study entry;
* A history of severe, life-threatening immune-mediated adverse events or infusion-related reactions during previous anti-tumor immunotherapy, including events that led to permanent discontinuation of treatment;
* Active infection (such as acute bacterial infection, tuberculosis, active hepatitis B/C, active syphilis, or active human immunodeficiency virus infection);
* Known allergy to other mAbs or any antibody excipients; the history of a severe allergic reaction, anaphylactoid or other hypersensitivity reactions to humanized antibodies or fusion proteins;
* A female who is pregnant or nursing;
* Patients were deemed unsuitable for participating in the study by the investigator for any reason.
A Phase 1 Dose Escalation and Dose Expansion Trial of KST-6051 in Participants With Advanced Solid Tumors With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation
KST-6051, an oral pan-KRAS inhibitor targeting both GTP- and GDP-bound KRAS mutant forms, is being tested alone or with other anticancer agents in a phase 1 dose escalation/expansion trial in adults with advanced or metastatic KRAS-mutant NSCLC, pancreatic, colorectal, or other solid tumors.
NCT07458347 · Phase 1 · Kestrel Therapeutics, Inc.
Recruiting sites: California, Florida, Massachusetts, Pennsylvania, Texas, Utah, Virginia
Read full eligibility criteria
Inclusion Criteria:
1. Age ≥ 18 years.
2. Willing and able to give written informed consent.
3. Histologically documented locally advanced and unresectable or metastatic NSCLC, PDAC, CRC, or other solid tumor.
4. Documentation of KRAS mutation prior to the first dose of trial drug(s).
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
6. Adequate cardiovascular, hematological, liver, and renal function.
7. Measurable disease at baseline per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).
Exclusion Criteria:
1. Central nervous system (CNS) tumors or untreated or unstable metastases.
2. Inability to swallow oral medications.
3. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
Other inclusion/exclusion criteria are specified in the protocol.
A Phase 1 Study Evaluating DISP-10 in Participants With Advanced Gastrointestinal Cancers
DISP-10, a combination of an oncolytic adenovirus (DV-10) followed by BCMA-directed CAR T-cell therapy (idecabtagene vicleucel) after lymphodepleting chemotherapy, is being studied in adults with advanced/metastatic gastrointestinal cancers including esophageal, gastroesophageal junction, gastric, colorectal, and biliary tract adenocarcinomas.
NCT07544589 · Phase 1 · Dispatch Biotherapeutics
Recruiting sites: California, Florida, Massachusetts, Ohio, Tennessee, Utah
Read full eligibility criteria
Key Inclusion Criteria:
1. Histologically confirmed advanced or metastatic esophageal, gastroesophageal junction, gastric adenocarcinoma, colorectal adenocarcinoma, or biliary tract carcinoma
2. Measurable disease according to RECIST v1.1 and at least 1 additional site of disease amenable to biopsy
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4. Aged ≥18 years at time of signing informed consent
5. Adequate organ function
Key Exclusion Criteria:
1. Previous solid organ or hematopoietic cell transplant
2. Evidence of rapid disease progression, defined as radiographic or clinical progression within 3 months of the most recent prior line of therapy
3. Known history of hepatitis B or HIV infection
4. Previous or concurrent malignancy except if curatively treated more than 3 years prior to enrollment
5. Known active central nervous system (CNS) metastases
6. Clinically significant pleural or pericardial effusion or peritoneal carcinomatosis
7. Active treatment with antiviral agents
8. History of severe hypersensitivity to fludarabine or cyclophosphamide
9. Prior therapies/treatments with oncolytic viruses or T cell derived cellular therapy
Additional criteria apply and should be discussed with the study site.