Background: To confirm synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment, we evaluated the effect of pretreatment with immune checkpoint inhibitors to ramucirumab plus irinotecan versus irinotecan in the third or later line treatment beyond progression after ramucirumab for advanced gastric cancer from the RINDBeRG trial. Methods: Patients received ramucirumab at 8 mg/kg plus irinotecan at 150 mg/m2 or irinotecan alone. End points were compared between treatment arms and pretreatments with nivolumab (NIVO+, n = 226) or without nivolumab (NIVO-, n = 169). Results: The overall survival hazard ratio was 0.84 (95 % confidence interval, 0.64-1.12) in the NIVO+ population and 1.05 (95 % confidence interval, 0.76-1.44) in the NIVO- population. The progression-free survival hazard ratio was 0.67 (95 % confidence interval, 0.51-0.87) in the NIVO+ population and 0.83 (95 % confidence interval,0.61-1.12) in the NIVO- population. The objective response rate was higher for ramucirumab plus irinotecan in both populations (NIVO+ population, 17.5 % vs 28.8 %; NIVO- population, 10.9 % vs 14.5 %). Safety profiles of the ramucirumab plus irinotecan arm were similar between populations. Conclusions: Progression-free survival and objective response rate improvements were observed for ramucirumab plus irinotecan in both populations and these benefits were enhanced with prior nivolumab therapy. Clinical trial information: jRCTs051180187.