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Background Nivolumab (Nivo) demonstrated survival benefit in previously treated gastric cancer (GC) patients (pts), with a response rate (RR) of 11% and a disease control rate (DCR) of 40% (Kang YK, et al. Lancet 2017). There are few real-world data of Nivo and its predictive markers are needed in GC. It has been demonstrated that the efficacy of anti-PD-1-based immunotherapy was associated with composition of gut microbiome in various types of cancers. Methods This observational/translational study (UMIN000030850) has been enrolling pts with advanced GC treated with Nivo alone and ECOG PS 0-2, up to 500 pts from March 2018. The aims are to evaluate the efficacy and safety of Nivo in real world, and to discover novel immune-related biomarkers (gut microbiome, genetic polymorphism, gene expression, and metabolome in plasma) using fecal and blood samples which are collected before and after treatment. Candidate factors will be explored in first 200 pts and then validated in last 300 pts. Pre-planned interim analysis was performed to evaluate response and biomarkers in first 200 pts. We report the response evaluated by first imaging based on RECIST version 1.1. Results In 198 evaluable pts (median age 70-y, 75% male, ECOG PS0/1/2 47%/39%/14%, 20% HER2-pos, tub/por/sig 47%/38%/6%), DCR was 34.8%. In 124 pts with measurable lesions, RR was 5.6% (95%CI 2.3-11.3): 7 PR, 34 SD, and 78 PD, and DCR was 33.1% (95%CI 24.9-42.1). Tumor growth rate (TGR) was calculated as a percentage increase in tumor volume during 1 month [Champiat et al. Clin Cancer Res 2017] in 105 evaluable pts. The TGR decreased after introduction of Nivo in 58.4% pts; however, 26 (24.8%) pts were identified as experiencing hyperprogressive disease which was defined as a ≥ 2-fold increase of the TGR before and after Nivo. Sub-analysis by patient background indicated that DCR was 38% for PS0, 35% for PS1, and 22% for PS2. In addition, the DCR was lower in pts with factors of signet-ring cell, peritoneal metastasis, or ascites. There was no difference in the DCR according to HER2 status or neutrophil-lymphocyte ratio. Conclusions This interim analysis of the observational trial showed real-world data of Nivo treatment in terms of response for advanced GC for the first time. Clinical trial identification UMIN000030850. Legal entity responsible for the study Japan Clinical Cancer Research Organization. Funding Ono pharmaceutical Co. Ltd. and Bristol-Myers Squibb. Disclosure Y. Sunakawa: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Yakult Honsha Co. Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd.; Honoraria (self), Research grant / Funding (institution): Sanofi K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Daiichi Sankyo Pharma; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Dainippon Sumitomo Pharm Co. Ltd.; Research grant / Funding (institution): Solasia Pharma K.K. M. Takahashi: Speaker Bureau / Expert testimony: Taiho Pharmaceutical Co. Ltd.; Speaker Bureau / Expert testimony: Eli Lilly and Company; Travel / Accommodation / Expenses: Takeda Pharmaceutical Co. Ltd. A. Makiyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lily Pharmaceutical; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co. Ltd.; Speaker Bureau / Expert testimony: Takeda Pharmaceutical Co. Ltd.; Speaker Bureau / Expert testimony: Taiho Pharmaceutical Co. Ltd. H. Yasui: Honoraria (self): Yakult Honsha; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Daiichi Sankyo company. H. Kawakami: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb Co. Ltd.; Honoraria (self), Advisory / Consultancy: Eli Lilly Japan K.K.; Honoraria (self), Advisory / Consultancy: MSD K.K.; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical Co. Ltd.; Honoraria (self), Advisory / Consultancy: Taiho Pharmaceutical Co. Ltd.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Bayer yakuhin Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (self): Daiichi Sankyo Co. Ltd.; Honoraria (self): Takeda Pharmaceutical Co. Ltd.; Research grant / Funding (self): Eisai Co. Ltd.; Research grant / Funding (self): Dainippon Sumitomo Pharmaceutical Co. Ltd. T.E. Nakajima: Honoraria (self): Nippon Kayaku Pharmaceutical Co. Ltd.; Honoraria (self): Teijin Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K; Honoraria (self): Celltrion Healthcare; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Eli Lilly Japan; Honoraria (self): Bristol-Myers Squibb Co. Ltd.; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Merck Serono; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Bayer yakuhin Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Sanofi K.K.; Honoraria (self): Sawai Pharmaceutical Co. Ltd.; Research grant / Funding (self), Research grant / Funding (institution): Daiichi Sankyo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Dainippon Sumitomo Pharm Co. Ltd.; Research grant / Funding (institution): Solasia Pharma K.K. K. Muro: Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Bristol-Myers Squibb Co. Ltd.; Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Takeda Pharmaceutical Co. Ltd.; Honoraria (self): Bayer yakuhin Ltd.; Honoraria (self), Research grant / Funding (self): Sanofi K.K.; Research grant / Funding (self): MSD K.K.; Research grant / Funding (self): Daiichi Sankyo Pharmaceutical Co. Ltd.; Research grant / Funding (self): Shionogi & Co. Ltd.; Research grant / Funding (self): Kyowa Hakko Kirin Pharmaceutical Co. Ltd.; Research grant / Funding (self): Gilead Sciences; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Merck Serono. R. Matoba: Shareholder / Stockholder / Stock options, Officer / Board of Directors: DNA Chip Research Inc. W. Ichikawa: Honoraria (institution), Speaker Bureau / Expert testimony: Taiho Pharmaceutical Co. Ltd.; Honoraria (institution): Takeda Pharmaceutical Co. Ltd; Honoraria (institution): Shionogi Pharmaceutical Co. Ltd.; Honoraria (institution): Ono Pharmaceutical Co. Ltd.; Honoraria (institution), Speaker Bureau / Expert testimony: Merck Serono; Honoraria (institution), Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co. Ltd. M. Fujii: Travel / Accommodation / Expenses: Taiho Pharmaceutical Co. Ltd.; Travel / Accommodation / Expenses: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.