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

Inclusion Criteria

• Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
• 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
• Participants receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility
• Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review
• 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