Background: Nivolumab (Nivo) has a significant survival benefit in salvage line of advanced gastric cancer (AGC) patients (pts) in ATTRACTION-2 trial. Based on synergistic anti-tumor effect induced by simultaneous blockade of PD-1 and VEGFR-2 in preclinical data, phase I/II study was conducted to investigate the safety and efficacy of Nivo plus ramucirumab (Ram) in the 2^nd line chemotherapy for AGC. Methods: AGC pts with measurable lesions, ECOG PS 0-1, disease progression on 1^st line chemotherapy containing platinum were eligible. Pts received Nivo (3mg/kg, Q2W) in combination with Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase I part), additional 40 patients were enrolled in a phase II part with the primary endpoint of a 6-months progression-free survival rate. Secondary endpoints included overall response rate, disease control rate, overall survival, and safety. PD-L1 tumor expression was assessed by immunohistochemistry (28-8 pharmDx assay) with a cut-off value for PD-L1 positivity set at 1% in tumor cells. Results: From 17-Jan-2017 to 31-Dec-2017, 46 AGC pts were enrolled. Patient characteristics were: median age 66 years, male 64%, ECOG PS1 40%, prior gastrectomy 35%, PD-L1 positive rate 44%. There were no dose limiting toxicities observed in phase I part. With median protocol treatment duration of 2.1 months, 40(87%) pts experienced any treatment-related AE (TRAE). Six (13%) pts had grade 3-4 TRAEs: hypertension (4%), hemorrhage (2%), colitis (2%), autoimmune pancreatitis (2%), liver dysfunction (2%), cholangitis (2%), hematoma (2%), and proteinuria (2%). There were no treatment-related deaths. Partial response was obtained in 10 (22%) pts with disease control rate (DCR) of 59%. With median follow-up time of 8.2 months, 20(44%) pts remain on treatment. Conclusions: Combination of Nivo and Ram showed no new safety signals and demonstrated promising antitumor activity in previously treated AGC. Clinical trial information: NCT02999295