New cancer drug candidate enters early human testing

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.