Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer

Inclusion Criteria

• Signed written informed consent.
• Age ≥ 18 years old (or minimum age based upon local regulations)
• Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric cancer. Gastric Cancer Expansion Phase will include only gastric cancer patients with 3+ HER2 positivity.
• HER2+ as 3+ (as defined in AJCC staging manual 8th edition) by IHC or in-situ hybridation (ISH) amplified.
• Have received prior treatment with trastuzumab.
• Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
• Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Measurable disease as per RECIST 1.1 criteria.

Exclusion Criteria

• Patients with symptomatic central nervous system (CNS) metastases.
• Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
• History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
• Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
• Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
• Treatment with corticosteroids (≥10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
• History of clinically-significant cardiovascular disease.
• Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
• History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
• Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
• Evidence of active viral, bacterial, or systemic fungal infection.