Nivo demonstrated survival benefit and a manageable safety profile in previously treated patients (pts) with GC or gastroesophageal junction (GEJ) cancer in a phase III trial (ATTRACTION-2), providing an objective response rate (ORR) of 11% and a disease control rate (DCR) of 40% (Kang YK, et al. Lancet 2017). Alternatively, about 60% of the pts did not respond to Nivo, raising the necessity of its predictive biomarkers. Routy B, et al. have demonstrated that the efficacy of anti-PD-1-based immunotherapy was associated with composition of gut microbiome in various types of cancers (Science 2017), but little is known about GC. Also, immune-related genetic polymorphisms have been shown to correlate with survival in GC pts (Sunakawa Y, et al. Pharmacogenomics J 2016). We therefore investigate whether host-related immune-factors will serve as predictors for Nivo in GC.
This is an observational/translational study to evaluate efficacy and safety of Nivo for advanced GC in real world, and to discover novel immune-related biomarkers for Nivo. We will enroll 500 pts treated with Nivo alone in any lines, and follow them for at least 2 years. Eligible pts must have: adenocarcinoma of the stomach or GEJ; recurrent or metastatic disease; ECOG PS 0-2; willing to undergo 2 collections of stool and blood before and at termination of the treatment. ORR, DCR, progression-free survival, overall survival, tumor shrinkage rate, and tumor progression rate are evaluated as the efficacy. Translational approach will be performed to identify host immune-related factors (gut microbiome, genetic polymorphism, gene expression, and metabolome in plasma) as predictors for efficacy and safety of Nivo, using fecal and blood samples. The samples will be collected before and after Nivo treatment. Candidate factors will be explored in first 200 pts and then validated in last 300 pts. An association of gut microbiome with efficacy of Nivo, primary endpoint of the approach, will be investigated by metagenomics analyses. Secondary endpoints include associations between immune-biomarkers and clinical outcomes of Nivo. Accrual is starting in March 2018.
Clinical trial identification
Legal entity responsible for the study
Ono Pharmaceutical and Bristol-Myers Squibb.
Y. Sunakawa: Honoraria: Merck Serono, Taiho Pharmaceutical, Chugai Pharma, Takeda, Yakult Honsha, Sanofi, Bayer Yakuhin, Ono Pharma, Bristol-Myers Squibb. K. Muro: Honoraria: Takeda, Chugai Pharma, Yakult Honsha, Merck Serono, Taiho Pharmaceutical, Lilly, Ono Pharma; Research funding: Ono Pharma, MSD, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Sciences. T.E. Nakajima: Consulting role: Taiho; Honoraria: Taiho, Lilly, Chugai, Kyowa Hakko Kirin, Takeda, Bristol-Myers Squibb, Ono, Bayer, Merck Serono; Research funding: Taiho, Lilly, Chugai, Kyowa Hakko Kirin, Takeda, Ono, MSD, Merck Serono, Yakult Honsha. H. Kawakami: Honoraria: Chugai Pharma, MSD, Lilly, Yakult Honsha, Ono Pharma, Taiho Pharma, Teueda, Merck Serono; Consulting role: Taiho Pharma, Teueda. E. Inoue: Speakers\' bureau: Merck Serono. R. Matoba: Leadership, stock and other ownership interests: DNA Chip Research. Y. Sato: Employment: DNA Chip Research. W. Ichikawa: Consulting role: Ono Pharma; Honoraria: Merck Serono, Taiho Pharma, Chugai Pharma, Takeda, Ono Pharma, Lilly. All other authors have declared no conflicts of interest.