Clinical Research Directory

Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 2. Part A: Histological diagnosis of one of the following unresectable locally advanced or metastatic solid tumors: * CRC, all subtypes * NSCLC: * Non-squamous cell carcinoma subtypes, such as adenocarcinoma * Squamous cell carcinoma subtype * Breast cancer (subtypes based on estrogen/progesterone receptor and HER2 testing according to American Society of Clinical Oncology - College of American Pathologists guidelines): * Triple-negative breast cancer * HR+, HER2- subtype * Esophageal, esophagogastric junction, and gastric cancer: * Adenocarcinoma subtype * Other histologies, if approved by the Medical Monitor, which may include: head and neck squamous cell carcinoma; cervical cancer; bladder cancer; squamous cell carcinoma subtype of esophageal, esophagogastric junction, and gastric cancer; HER2+ breast cancer 3. Part B Cohorts - Histological diagnosis of one of the following unresectable locally advanced or metastatic solid tumors: * Cohort B1: CRC, all subtypes * Cohort B2: NSCLC * Non-squamous cell carcinoma subtypes, such as adenocarcinoma * Squamous cell carcinoma subtype * Cohorts B3 and B4: Cohort-specific disease indications may include those listed for Part A 4. Participants must have disease that is considered to be noncurative and meet the appropriate criteria below: * Part A only: Participants have progressed on, were intolerant to, or have a contraindication to prior SOC treatments, with no satisfactory SOC treatment options available. * Part B only: * Cohort B1 (CRC): * Participants must have previously progressed on, were intolerant to, or have a contraindication to fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, bevacizumab, and for those with RAS wild-type tumors, an anti-epidermal growth factor receptor (EGFR)-directed monoclonal antibody in advanced disease setting. * Participants with actionable biomarkers must have been treated with at least one prior appropriate biomarker-directed therapy. * If any of these therapies were given in the adjuvant setting, disease must have progressed within 6 months after completing therapy. * Participants must not have received more than 3 prior lines of systemic therapy (excluding targeted therapies for actionable biomarkers). * Cohort B2 (NSCLC): * Participants must have previously progressed on, were intolerant to, or have a contraindication to platinum-based chemotherapy and a programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibody (given concurrently or sequentially with chemotherapy) in advanced disease setting. * Participants with actionable biomarkers must have been treated with at least one prior appropriate targeted therapy. * If any of these therapies were given in the adjuvant setting, disease must have progressed within 6 months after completing therapy. * Participants must not have received more than 2 prior lines of systemic therapy (excluding targeted therapies for actionable biomarkers). * Cohorts B3 and B4: Criteria will be specified based on the disease indications selected. 5. Participants must have measurable disease as defined per RECIST v1.1 Exclusion Criteria: 1. Previously treated with an antibody-drug conjugate (ADC) with a topoisomerase-1 (TOP1) inhibitor payload. Exception: Participants with NSCLC or breast cancer may have received up to one prior ADC with a TOP1 inhibitor payload 2. History of anaphylactic reaction to TOP1 inhibitors (e.g., irinotecan) or TOP1 inhibiting ADCs 3. Life expectancy \< 12 weeks 4. Prior solid organ transplant 5. Symptomatic ascites or pleural effusion 6. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis 7. Known history of another primary solid or hematologic malignancy (other than that under study), unless the participant has undergone definitive/curative therapy, has had no evidence of recurrence and has negligible risk of metastatic disease of death, with approval by the Medical Monitor