Study to Assess the Efficacy and Safety of Rina-S in Participants With Advanced Gastrointestinal (GI) Cancers

This is a Phase 2, open-label, multicenter, multi-cohort trial to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics of Rina-S as monotherapy in participants with GI cancers who have progressed on or after prior standard of care (SoC) therapies.

Key Inclusion Criteria:

• All study cohorts

• Participant has histologically or cytologically confirmed GI cancer.
• Participant has documented metastatic or unresectable disease, not amenable to treatment with curative intent.
• Participant has measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at baseline.
• Participant must have radiological disease progression while on or after receiving the most recent regimen.
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participant has life expectancy ≥3 months.
• Participant must be able to provide a newly obtained or archival tissue sample.
• Participant must have adequate organ and bone marrow function, per laboratory test results prior to Rina-S administration.

Key Exclusion Criteria (all study cohorts):

• Participant has clinically significant non-malignant gastrointestinal disorders, including but not limited to, diarrhea > grade 1, ulcerative colitis, inflammatory bowel disease.
• Participants with recent (up to 4 weeks) history of significant gastrointestinal bleeding, current cancer related ulcerations, fistula, abscess or recent perforation (within 4 to 6 weeks).
• Participant has a past or current malignancy other than the inclusion diagnosis before the planned first dose of trial treatment, or any evidence of residual disease from a previously diagnosed malignancy.
• Participants with newly identified or known unstable (eg, progressing brain metastases) or symptomatic central nervous system (CNS) metastases or history of carcinomatous meningitis (also known as leptomeningeal disease).
• Prior treatment with topoisomerase-1 inhibitor containing antibody-drug conjugate (ADC).
• Treatment with an anticancer agent within 28 days prior to the first dose of trial treatment.

Note: Other protocol-defined Inclusion and Exclusion criteria may apply.