Background: Gastric cancer is a prevalent worldwide disease for which surgical resection alone is insufficient to cure the majority of localized patients. Peri-operative chemotherapy is a standard of care approach that has demonstrated modest improved survival rates. Immune checkpoint therapy has proven efficacy in a subset of patients with refractory disease but it’s role in earlier stage disease and in combination with chemotherapy is not defined. By combining chemotherapy with immune checkpoint blockade utilizing pembrolizumab we hypothesize that we will obtain improved tumor response and prolonged disease control compared to chemotherapy alone. Tissue specimens will be obtained at baseline and at the time of surgery for novel correlative studies including single cell T cell receptor characterization and expression profiling. Methods: This Phase 2, multicenter study investigates the efficacy and safety of oxaliplatin/FU based chemotherapy plus pembrolizumab in the perioperative treatment of locally advanced, resectable gastric or GE junction adenocarcinoma. A total of 40 eligible patients with T2-4 and/or N1, M0 tumors on imaging or EUS will be treated with capecitabine, oxaliplatin and epirubicin (epirubicin can be omitted at investigator discretion) plus fixed dose pembrolizumab at 200mg for 3 cycles prior to surgery plus one additional dose of pembrolizumab alone before surgery. Following completion of post-operative chemotherapy with pembrolizumab, patients continue pembrolizumab for 1 year of maintenance therapy (17 cycles). The primary endpoint is disease free survival at 24 months (DFS 24) with an estimated 80% power to detect a clinically significant 24 month DFS rate of 65%. A key secondary endpoint is pathCR at surgery, additional endpoints include response rate (RECIST 1.1), 12 month DFS, and overall survival. Safety, including surgical outcomes, will be assessed. Multiple correlative analyses utilizing baseline and post-treatment tissue, PD-L1 staining, and serum samples will also be performed. Enrollment opened in March 2017. Clinical trial information: NCT02918162