Nivolumab (NIVO) in patients (pts) with advanced (adv) chemotherapy-refractory (CT-Rx) esophagogastric (EG) cancer according to microsatellite instability (MSI) status: checkmate 032

Abstract

Background: NIVO improved OS vs placebo in Asian pts with gastric/gastroesophageal junction cancer in the phase 3 ATTRACTION-2 study (Kang YK, et al. ASCO GI 2017 [abstract 2]). In CheckMate 032, NIVO6ipilimumab (IPI) demonstrated ORRs of 14% (NIVO monotherapy) and 26% (NIVO 1 mg/kg + IPI 3 mg/kg) in CT-Rx EG cancer (NCT01928394; Janjigian YY, et al. ASCO 2017 [abstract 4014]). The Cancer Genome Atlas identified MSI-high (MSI-H) EG tumors as having therapeutic targets that may make them responsive to immune checkpoint inhibitors. This exploratory analysis evaluated ORR and OS by MSI status in pts with EG cancer treated with NIVO monotherapy in CheckMate 032. Methods: Pts with adv CT-Rx EG (including gastric, esophageal, and gastroesophageal junction) cancerwere treated with NIVO3mg/kg every 2 weeks (n=59). MSI status was centrally assessed using a PCR-based assay. Best objective response (BOR),ORR, and DCR (BOR of CR, PR, or SD) per investigator (INV) were assessed per RECIST v1.1. Results: MSI status was determined in 25 pts; 7 (28%) were MSI-H, and 18 (72%) were non-MSI-H. ORR per INV was 29% in MSI-H pts, 11% in non-MSI-H pts, and 9% in pts with unknown MSI (MSI-U). DCR was 71%, 28%, and 26%, respectively. Of the 7 responders, 3 were PD-L1+ (≥1% tumor expression; 1 per MSI category), 3 were PDL1 ≤ (MSI-U, n=2; non-MSI-H, n=1), and 1 was not evaluable for PD-L1 assessment (MSI-H). BOR is shown in the Table. Median OS (95% CI) was 14.75 mo (1.51, NA) in MSI-H pts, 6.49 mo (2.96, 12.42) in non-MSI-H pts, and 5.03 mo (2.76, 16.16) in MSIU pts. Safety for the full EG cohort was previously reported (Janjigian YY, et al. ASCO 2016 [abstract 4010]). Conclusions: In this subgroup analysis, 7 pts (28%) were MSI-H, representing a biologically unique subset of EG tumors. NIVO monotherapy led to survival benefit and responses in both MSI-H and non-MSI-H pts. (Table Presented).