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