KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

Inclusion Criteria: * Histologically and/or cytologically documented and radiographically measurable (by RECIST 1.1) adenocarcinoma of the esophagus or stomach (HER2-positive or negative) that is metastatic/recurrent and not amenable to potentially curative treatment * No prior chemotherapy for metastatic/recurrent disease. Prior adjuvant or neo-adjuvant treatment with a fluoropyrimidine or fluoropyrimidine based regimen is allowed only if it is completed at least 6 months prior to the start of study drug, whether given alone or with radiation therapy. Patients who have received prior neo-adjuvant therapy (chemotherapy and/or radiation therapy) which did not contain 5-FU or capecitabine and have been diagnosed with metastatic disease (with no previous treatment in the metastatic setting) are eligible. No 6-months window is required for these patients. In the setting of metastatic disease requiring local palliation, only radiosensitizing doses of 5-FU or capecitabine monotherapy are permitted. * Prior radiation therapy is permitted, provided is completed at least 28 days prior to the start of study drug. * Age ≥ 18 years with ability to understand and willingness to provide informed consent. * ECOG performance status of 0 or 1. * Adequate organ and marrow function as defined below by the following: 1. Absolute neutrophil count (ANC) ≥ 1500 µl 2. Platelets ≥ 100,000/µl 3. Hemoglobin (Hgb) ≥ 9 g/dL 4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) 5. AST/ALT ≤ 2 x ULN without liver metastasis; ≤ 5 x ULN with liver metastasis 6. Creatinine clearance ≥ 50 cc/min Exclusion Criteria: * Prior therapy with an anti-PD-1, anti PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents. * Chemotherapy, targeted small molecule therapy, radiotherapy, experimental agents, prior therapy with anti-tumor vaccines or other immune-stimulatory antitumor agents, or biological cancer therapy (including monoclonal antibodies) within 14 days prior to the start of study drug, or not recovered (≤ grade 1 or baseline) from adverse events due to a previously administered agent. * Known CNS metastases and/or carcinomatous meningitis. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 30 days prior to the start of study drug. * Documented history of clinically significant autoimmune disease (other than well-controlled hypothyroidism) or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Receiving systemic steroid therapy or any form of immunosuppressive therapy within 1 week prior to the start of study drug. * Received a live vaccine within 4 weeks prior to the start of the study drug. * Has known history of, or any evidence of active, non-infectious pneumonitis. * Known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible. * Pregnant or breastfeeding * Not willing to use an effective method of birth control * Concurrent severe and/or uncontrolled medical conditions, which may compromise participation in the study, including impaired heart function or clinically significant heart disease. * Current use of medication specified by the protocol as prohibited for administration in combination with the study drug. This includes patients with a condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the start of study drug. Inhaled or topical steroids and adrenal replacement doses \> 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. * Recent or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment within 2 weeks prior to the start of study drug. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study (except fot rhe planned metastatectomy). * Serious, non-healing wound, ulcer, or bone fracture. * History of myocardial infarction, NYHA lass III or IV congestive heart failure, arrhythmia requiring therapy, unstable angina, cardia or other vascular stenting, angioplasty, or surgery within 6 months prior to the start of study drug. * History of other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with a current PSA of \< 1.0mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to the start of study drug.