ATTRACTION-04 (ONO-4538-37): A randomized, multicenter, phase 2/3 study of nivolumab (Nivo) plus chemotherapy in patients (Pts) with previously untreated advanced or recurrent gastric (G) or gastroesophageal junction (GEJ) cancer

[[abstract]]Background: Nivo, a fully human IgG4 programmed death 1 (PD-1) immune checkpoint inhibitor, has demonstrated survival benefits across a number of tumor types. In ATTRACTION-02 (ONO-4538-12), a double-blind, placebo-controlled, Phase 3 study in pts with unresectable advanced or recurrent G/GEJ cancer refractory to or intolerant of standard therapy, Nivo monotherapy (3 mg/kg Q2W) demonstrated survival benefits (overall survival [OS] and progression free survival [PFS]) vs. placebo and a manageable safety profile (Yoon-Koo Kang, et al. 2017 ASCO Gastrointestinal Cancers Symposium). The combination fluoropyrimidine and platinum is the current standard-of-care (SOC) in the first-line treatment of pts with metastatic G/GEJ cancer that generally achieves a median survival ranging between 11 and 13 months. Therefore, new treatment options are needed to further improve the clinical outcomes of this particular pts population. This multinational, randomized, Phase 2/3 trial will evaluate the efficacy and safety of Nivo plus chemotherapy (S-1 + oxaliplatin [SOX] or capecitabine + oxaliplatin [CapeOX]) as first-line therapy for pts with unresectable advanced or recurrent G/GEJ cancer (ATTRACTION-04; NCT02746796). Trial design: This trial consists of two parts. The part 1 is a randomized, open-label study to assess the feasibility of Nivo in combination with the first-line chemotherapy, either SOX or CapeOX. In part 2, approximately 650 chemo-naïve pts aged ≥ 20 years with ECOG PS 0-1, and HER2 negative unresectable or recurrent G/GEJ cancer will be randomized to receive chemotherapy (SOX or CapeOX, investigator’s choice) plus either Nivo or Placebo. Randomization will be stratified by intensity of PD-L1 expression, ECOG PS score, disease status and geographical region. Primary endpoints are PFS assessed by independent radiological review committee (IRRC) and OS. Secondary endpoints include objective response rate and disease control rate assessed by IRRC and the site investigator, and duration of response and time to response assessed by IRRC. The part 2 study was started in February 2017