Abstract CT078: First-line treatment with sintilimab (sin) vs placebo in combination with chemotherapy (chemo) in patients (pts) with unresectable gastric or gastroesophageal junction (G/GEJ) cancer: Final overall survival (OS) results from the randomized, phase III ORIENT-16 trial

Abstract Background: The phase III ORIENT-16 trial evaluated sin (a PD-1 inhibitor) versus placebo plus chemo as first-line (1L) treatment in pts with advanced G/GEJ adenocarcinoma. Sin+chemo previously showed a significant improvement in OS vs chemo in pts with PD-L1 combined positive score (CPS) ≥5 (HR 0.660; 95% CI 0.505-0.864; P=0.0023) and in all pts (HR 0.766; 95% CI 0.626-0.936; P=0.0090), with a median follow-up of 18.8 months (m) at interim analysis (Xu, et al. Ann Oncol 2021). Here we report the results from the final analysis (NCT03745170). Methods: This double-blind, phase III trial enrolled 650 pts ≥18 years of age with untreated, unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma, regardless of PD-L1 expression. Pts were randomized 1:1 to receive sin (3 mg/kg in pts weighing <60 kg or 200 mg in pts weighing ≥60 kg, IV Q3W) or placebo plus chemo (oxaliplatin 130 mg/m2 IV Q3W for up to 6 cycles, capecitabine 1000 mg/m2 PO Bid d1-14 Q3W) for 24 months. The primary endpoints were OS in pts with CPS ≥5 and all randomized pts. The data cutoff date for the final analysis was Sep 2, 2022. Results: With a median follow-up of 33.9 m, sin+chemo continued to show OS benefit over chemo in all pts (15.2 vs 12.3 m; HR 0.681 [95% CI: 0.571, 0.812]; P<0.0001); estimated OS rates at 24 and 36 m for sin+chemo vs chemo were 37.6% vs 20.6% and 26.0% vs 10.7%, respectively. OS benefits with sin+chemo vs chemo across subgroups were generally consistent with the previous report. The updated PFS was superior with sin+chemo vs chemo (HR 0.638, 95% CI 0.530-0.768; P<0.0001). The updated confirmed ORR per RECIST v1.1 was 58.2% vs 48.8% in all pts with measurable disease at baseline, with a median DoR of 9.9 vs 7.0 m, respectively; 47.8% of responders in sin+chemo group and 25.9% of responders in chemo group had DoR ≥12 m. In pts with CPS ≥5, significant OS benefit (median OS 19.2 vs 12.9 m; HR 0.587 [95% CI: 0.467, 0.738]; P<0.0001) and superior PFS (HR 0.621, 95% CI 0.490-0.787; P<0.0001) with sin+chemo over chemo remained. A delayed numerical OS improvement was observed for subgroup pts with CPS <5. No new or unexpected safety signals were identified. Conclusion: The previously reported significant OS benefit with sin+chemo vs chemo was more evident in CPS ≥5 pts and in all pts with 15 m of additional follow-up, further confirming sin+chemo as a standard of care for 1L treatment of G/GEJ adenocarcinoma. Citation Format: Jianming Xu, Haiping Jiang, Yueyin Pan, Kangsheng Gu, Shundong Cang, Lei Han, Yongqian Shu, Jiayi Li, Junhui Zhao, Hongming Pan, Suxia Luo, Yanru Qin, Qunyi Guo, Yuxian Bai, Yang Ling, Yingmei Guo, Yuling Chen, Yan Wang, Hui Zhou. First-line treatment with sintilimab (sin) vs placebo in combination with chemotherapy (chemo) in patients (pts) with unresectable gastric or gastroesophageal junction (G/GEJ) cancer: Final overall survival (OS) results from the randomized, phase III ORIENT-16 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT078.