First-Line Sugemalimab Plus Chemotherapy for Advanced Gastric Cancer
Authors: Xiaotian Zhang, Jufeng Wang, Gang Wang, Yanqiao Zhang, Qingxia Fan, Chuangxin Lu, Changlu Hu, Meili Sun, Yiye Wan, Sanyuan Sun, Junye Wang, Li Zhang, Yongqian Shu, Jie Luo, Dan Zhu, Zhenwei Shen, Sheng Yao, Qingmei Shi, Jason Yang, Lin Shen, Yanru Xie, Xiaoyan Lin, Jiayi Li, Yunpeng Liu, Ruixing Zhang, Li Xiao, Ping Chen, Xinhui Yang, Zishu Wang, Zhanxiong Luo, Qi Li, Yanrong Gao, Qi Wang, Jianping Xiong, Ting Fu, Yan Lin, Zhong Xie, Yunbo Zhao, Yiping Mou, Tao Zhang, Wangjun Liao, Yinping Sun, Dong Yan, Yanxia Ji, Hongxia Li, Yongquan Shi, Hongming Pan, Yanhong Deng, Yanhua Chen, Juntao Yao, Anji Hou, Xinjun Liang
Journal: JAMA (2025)

Importance Gastric cancer, including gastroesophageal junction cancer, is one of the most commonly diagnosed cancers worldwide, with high mortality. Sugemalimab is a fully human anti–programmed death-ligand 1 (PD-L1) antibody. The combination of sugemalimab and chemotherapy showed promising antitumor activity and safety in a phase 1b study among patients with treatment-naive, unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. This combination was further evaluated in the GEMSTONE-303 phase 3 trial. Objective To evaluate the efficacy of sugemalimab in combination with capecitabine and oxaliplatin (CAPOX) compared with placebo plus CAPOX as first-line treatment for patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 combined positive score (CPS) of 5 or greater. Design, Setting, and Participants GEMSTONE 303 is a phase 3, randomized, double-blind, placebo-controlled study conducted at 54 sites in China that enrolled patients from April 9, 2019, through December 29, 2021, with follow-up to July 9, 2023. A total of 479 eligible patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 CPS of 5 or greater who did not receive any prior systemic therapy were randomized. Intervention Patients received sugemalimab (1200 mg intravenously) (n = 241) or placebo (n = 238) every 3 weeks for up to 24 months, plus CAPOX every 3 weeks for up to 6 cycles. Main outcomes and Measures Primary outcomes were overall survival and investigator-assessed progression-free survival. Results Baseline characteristics were well balanced between the 2 groups. Most patients were male (71.4% in sugemalimab group, 74.8% in placebo group). Median follow-up was 25.1 months in the sugemalimab group and 26.3 months in the placebo group. The sugemalimab group demonstrated significant improvements in overall survival (median, 15.6 months [95% CI, 13.3-17.8] vs 12.6 months [95% CI, 10.6-14.1]; hazard ratio, 0.75 [95% CI, 0.61-0.92]; P = .006) and progression-free survival (median, 7.6 months [95% CI, 6.4-7.9] vs 6.1 months [95% CI, 5.1-6.4]; hazard ratio, 0.66 [95% CI, 0.54-0.81]; P &amp;amp;lt; .001). Grade 3 or higher treatment-related adverse events occurred in 53.9% of patients in the sugemalimab group and 50.6% in the placebo group. Conclusions and Relevance Sugemalimab plus chemotherapy significantly prolonged overall survival and progression-free survival with a manageable safety profile in previously untreated patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. Trial Registration ClinicalTrials.gov Identifier: NCT03802591