A Randomized, Open-Label, Multicenter Phase 3 Trial of Domvanalimab, Zimberelimab, and Chemotherapy Versus Nivolumab and Chemotherapy in Participants With Previously Untreated Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma

Inclusion Criteria:

• Age >= 18 years at the time of signing the informed consent.
• Capable of giving signed informed consent which is in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.
• Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
• At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Exclusion Criteria:

• Underlying medical or psychiatric conditions that, in the investigator's or sponsor's opinion, will make the administration of study-specified therapy hazardous, including but not limited to:
  • Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization.
  • Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization.
  • History of prior solid-organ transplantation, including allogenic bone marrow transplantation.
  • Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial.
• Known human epidermal growth factor receptor 2 (HER-2) positive tumor.
• Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
• Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
• Disease progression within 6 months of neoadjuvant or adjuvant chemotherapy.