🧪 Newly & Currently Recruiting Trials

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: * 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

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