First-Line (1l) Nivolumab (Nivo) Plus Chemotherapy (Chemo) Versus Chemo In Patients (Pts) With Advanced Gastric Cancer/Gastroesophageal Junction Cancer/Esophageal Adenocarcinoma (Gc/Gejc/Eac): Checkmate 649 Chinese Subgroup Analysis.

Abstract Background: Overall survival (OS) for advanced or metastatic HER2-negative GC/GEJC with standard 1L chemo remains poor (median OS < 1 year). CheckMate 649 is the largest randomized, global phase 3 study of 1L programmed death (PD)-1 inhibitor-based therapies in GC/GEJC/EAC (NCT02872116). Results from this study demonstrated superior OS, along with progression-free survival (PFS) benefit and an acceptable safety profile with 1L NIVO + chemo vs chemo alone (Moehler et al. Ann Oncol 2020). We present the pre-planned subgroup analysis from CheckMate 649 in Chinese pts.Methods: Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD ligand 1 (PD-L1) expression. Pts with known HER2-positive status were excluded. Pts were randomized to receive NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded central review in pts with PD-L1 combined positive score (CPS) ≥ 5.Results: 208 Chinese pts were concurrently randomized to NIVO + chemo or chemo, including 156 pts (75%) with PD-L1 CPS ≥ 5. Median age was 60 years; 88% had GC; 12% had GEJC; no pts had EAC. At minimum follow-up of 12 months (mo), NIVO + chemo demonstrated clinically meaningful improvement in OS and PFS vs chemo in pts with PD-L1 CPS ≥ 5 (OS, HR 0.54 [95% CI 0.36-0.79]; PFS, HR 0.52 [0.34-0.77]; Table), consistent with the overall study population. OS benefit was also observed in pts with PD-L1 CPS ≥ 1 and the all-randomized population (Table). No new safety signals were identified. Conclusions: NIVO + chemo demonstrated a clinically meaningful improvement in OS and PFS and an acceptable safety profile vs chemo alone in previously untreated Chinese pts, consistent with the overall study population with advanced GC/GEJC/EAC from CheckMate 649. TableEfficacyNIVO + chemoChemoPD-L1 CPS ≥ 5N = 75N = 81Median OS (95% CI), mo15.5 (11.9-25.5)9.6 (8.0-12.1)HR (95% CI)0.54 (0.36-0.79)Median PFS (95% CI), mo8.5 (5.9-12.4)4.3 (4.1-6.5)HR (95% CI)0.52 (0.34-0.77)ORR (95% CI), %63 (51-74)43 (32-55)PD-L1 CPS ≥ 1N = 89N = 94Median OS (95% CI), mo14.3 (11.5-17.5)9.9 (8.1-12.1)HR (95% CI)0.62 (0.43-0.87)All randomizedN = 99N = 109Median OS (95% CI), mo14.3 (11.5-17.5)10.3 (8.1-12.1)HR (95% CI)0.61 (0.44-0.85)Safety: Treatment-related adverse events, n (%)All treatedN = 99N = 106Any grade98 (99)100 (94)Grade 3-464 (65)53 (50)Leading to discontinuation50 (51)27 (25)Deaths1 (1)1 (<1) Citation Format: Lin Shen, Yuxian Bai, Xiaoyan Lin, Wei Li, Jufeng Wang, Xiaochun Zhang, Hongming Pan, Chunmei Bai, Li Bai, Ying Cheng, Jingdong Zhang, Haijun Zhong, Yi Ba, Wenwei Hu, Ruihua Xu, Weijian Guo, Shukui Qin, Nong Yang, Jianwei Lu, Kohei Shitara, Ming Lei, Mingshun Li, Nicole Bao, Tian Chen, Tianshu Liu. First-Line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate 649 Chinese subgroup analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT184.