The purpose of this study is to evaluate the safety and preliminary clinical activity of treatment combinations with and without chemotherapy in participants with locally advanced unresectable or metastatic gastric, GEJ, and esophageal adenocarcinoma. Chemotherapy will consist of FOLFOX (oxaliplatin, leucovorin, fluorouracil).

Key Inclusion Criteria:

• Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3 months as assessed by the Investigator
• Eastern cooperative oncology group (ECOG) Performance Score of 0-1
• At least one measurable target lesion per RECIST v1.1.
• Adequate organ and marrow function
• Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing

Key Exclusion Criteria:

• Participants with underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational products hazardous
• Only for Cohort A: Known Human Epidermal Growth Factor Receptor 2 (HER-2) positive tumor
• Known untreated, symptomatic, or actively progressing central nervous system (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
• Discontinued use of prior immune checkpoint therapy due to immune related adverse events; received prior treatment with an anti-TIGIT monoclonal antibody.
• History of trauma or major surgery within 28 days prior to enrollment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

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