Background: Localized gastric cancer is a potentially curable condition and long-term outcomes depend on YP staging. Currently, preferred adjunctive therapy depends on geographic location. Preliminary data from NCT01928394 have shown promising clinical activity of immunotherapy (IO) agents nivolumab (nivo) +/- ipilimumab (ipi) in the metastatic setting. We conducted a single-arm study using IO + chemotherapy followed by immune-chemoradiation prior to surgery, followed by adjuvant IO, in patients with localized gastric adenocarcinoma. Our primary objective was to determine safety and toxicity with this approach. Secondary objectives included efficacy by YP staging and R0 resection rate. Methods: Patients with localized gastric adenocarcinoma were enrolled into NCT03776487 (n=30). Participants received the following: (1) biweekly chemotherapy with 4 doses of 5-Fluorouracil (5-FU)/Oxaliplatin, (2) nivo 240mg q2weeks (x3) and ipi 1mg/kg q6weeks (x1), (3) immune-chemoradiation (biweekly nivo + 5FU Mon-Fri concurrently with a total of 45 Gy given in 25 fractions), and (4) surgical resection. Those with residual disease received adjuvant nivolumab monthly for 6 doses. Correlative studies are planned. To assess preliminary efficacy, the clinical and pathologic complete response rates (pCR) were estimated along with the corresponding exact 95% confidence interval. Adverse events and toxicities were summarized using descriptive statistics. Results: Median follow-up was 27.4 months at the time of data cutoff. Of 30 enrolled, 23 patients completed surgery and seven did not due to progression of disease(n=5) and worsening co-morbidities(n=2). The side effect profile was similar to prior IO studies, with no grade 5 events observed. Three patients (10%) experienced grade 4 events (acute kidney injury, myocarditis, and neutropenia). The most frequent grade 3 toxicity was nausea and vomiting (10%). From the 23 participants that underwent resection, 22 had pathologic data at the time of analysis, with 9 achieving ypT0ypN0 (40.9%, 95% CI: 20.7%, 63.7%). There was an 86% R0 resection rate. Conclusions: Our results are encouraging and support further development of this strategy for localized gastric adenocarcinomas. The regimen is safe and potentially generalizable. Clinical trial information: NCT03776487.