Pembrolizumab, Oxaliplatin, Capecitabine as First Line Treatment for Patients with Recurrent or Metastatic Esophagus or Stomach Cancer

Inclusion Criteria

• Histologically and/or cytologically documented and radiographically measurable (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) adenocarcinoma of the esophagus or stomach (HER2 negative only) that is metastatic/recurrent and not amenable to potentially curative treatment (e.g., inoperable metastatic or locally recurrent disease); HER2 positive patients would be considered eligible only if there is a contraindication to Herceptin
• 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 fluorouracil (5-FU) or capecitabine and have been diagnosed with metastatic disease (with no previous treatment in the metastatic setting) are eligible; no 6-month 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 it is completed at least 28 days prior to the start of study drug
• Ability to understand and willingness to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1500 ul
• Platelets >= 100,000/ul
• Hemoglobin (Hgb) >= 9 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 x ULN without liver metastasis; =< 5 x ULN with liver metastasis
• 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, 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 central nervous system (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 for treatment of CNS lesion 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; Note: patients are permitted to receive up to 12 mg dexamethasone dose prior to administration of oxaliplatin and low dose steroids for up to 48 hours after dosing to prevent nausea and vomiting
• Received a live vaccine within 4 weeks prior to the start of study drug
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Known history of human immunodeficiency virus (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 medications specified by the protocol as prohibited for administration in combination with study drug; this includes patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg 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 > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; corticosteroids administered as pre-medication for IV contrast allergy are also allowed
• Recent or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment within 2 weeks prior to the start of study drug. Subjects being treated for Helicobactor pylori infection are an exception and are allowed to start protocol based therapy while still on antibiotics
• 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 for the planned metastasectomy)
• Serious, non-healing wound, ulcer, or bone fracture
• History of myocardial infarction, New York Heart Association (NYHA) class III or IV congestive heart failure, unstable angina, cardiac 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 < 1.0 mg/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