Key Inclusion Criteria:
General Inclusion Criteria (all cohorts):
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable disease per RECIST version 1.1
- Adequate hematology, renal and hepatic function
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Patients with brain metastases may be enrolled only if treated, nonprogressive, asymptomatic and not taking high dose steroids for at least 4 weeks prior to Cycle 1 Day 1 (C1D1)
- Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception, per protocol.
- Tissue criteria: must provide sufficient, and adequate tumor tissue sample or agree to have a biopsy taken.
Part A Specific Inclusion Criteria: zamzetoclax as monotherapy
- Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor for which no standard therapy is available, standard therapy has failed, or for whom standard-of-care therapy is contraindicated.
Cohorts B1 and C1 Specific Inclusion Criteria:
- Histologically or cytologically confirmed unresectable metastatic or locally advanced disease following treatment for metastatic disease including an immune checkpoint inhibitor and a platinum-containing chemotherapy
- Patients with actionable genomic alterations must have also received treatment with at least 1 approved therapy appropriate to the genomic alteration unless unavailable or contraindicated
Cohorts B4 and C4 Specific Inclusion Criteria:
- Histologically or cytologically confirmed disease based on the most recent analyzed biopsy metastatic disease that is refractory to or relapsed after at least 2 prior standard-of-care chemotherapy regimens, one of which was a taxane (unless contraindicated).
Key Exclusion Criteria:
- Prior systemic anti-cancer therapy must meet wash-out criteria outlined in protocol
- Treatment with any high dose systemic corticosteroids or nonsystemic radiotherapy within 2 weeks of the first dose of zamzetoclax (low dose corticosteroids permitted).
- Women who are pregnant or lactating
- Patients with active ≥ Grade 2 nausea or vomiting, and/or signs of intestinal obstruction
- Known active or chronic hepatitis B or C infection or HIV infection/ HIV positive
- Known history of clinically significant cardiovascular disease or heart failure.
- Known history of clinically significant active chronic obstructive pulmonary disease or other moderate to severe chronic respiratory illness present within 6 months prior to C1D1
- Known history of other clinically significant pulmonary disease or evidence of active pneumonitis
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- History of clinically significant bleeding, intestinal obstruction, or gastrointestinal (GI) perforation within 6 months prior to C1D1
- Infection requiring intravenous anti-infective use within 2 weeks prior to C1D1
- Active or history of autoimmune disease or immune deficiency
- History of uncured coexisting cancer, not including uncured basal cell carcinoma, cervical cancer in situ, or superficial bladder cancer.
Cohort A Specific Exclusion Criteria: zamzetoclax as monotherapy:
- Known heart failure or elevated cardiac biomarkers
Cohorts B1 and C1 Specific Exclusion Criteria:
- Known hypersensitivity to excipients in study treatments.
Cohorts B4 and C4 Specific Exclusion Criteria:
- Prior treatment with sacituzumab govitecan-hziy or a topoisomerase 1 inhibitor or agents targeting Trop-2.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.