An observational/translational study for nivolumab treatment in advanced gastric cancer: JACCRO GC-08 (DELIVER trial)

Abstract

Background: Nivolumab (Nivo) demonstrated survival benefit and a manageable safety profile in previously treated patients (pts) with gastric cancer (GC) or gastroesophageal junction (GEJ) cancer in the ATTRACTION-2 trial, providing an objective response rate (ORR) of 11% and a disease control rate (DCR) of 40% (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 (Science 2017), but little is known about GC. We therefore investigate whether host-related immunefactors will serve as predictors for Nivo in GC. Trial design: 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. It has been enrolling pts with advanced GC treated with Nivo alone in any lines, up to 500 pts from March 2018. 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 in the study. 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 evaluated by first imaging, primary endpoint of the approach, will be investigated using metagenomics analyses. Secondary endpoints include associations between other immune-biomarkers and clinical outcomes of Nivo (UMIN000030850).