🧪 Newly & Currently Recruiting Trials

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.

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

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

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

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