Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer

Key Inclusion Criteria: * Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma 1. Prior systemic perioperative treatment is allowed; however the participants must have had a disease-free interval of at least 6 months from end of chemo/surgery 2. Participants receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility 3. Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review 4. Cohort B: HER2-positive (by IHC 3+ or IHC 2+ in combination with FISH+) by local review. PD -L1 status is not required for enrollment. * Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or contemporaneous biopsy for tumor target testing * Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3 days of Day 1 * Life expectancy ≥ 6 months * At least one radiographically measurable target lesion * Acceptable laboratory parameters and adequate organ function Key Exclusion Criteria: * Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions * Participants with known MSI-H status * History of allogeneic stem cell or tissue/solid organ transplant * Central nervous system metastases * Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary compromise * Prior neoadjuvant or adjuvant treatment with immunotherapy