First-Line Sugemalimab Plus Chemotherapy for Advanced Gastric Cancer
Authors: Zhang Xiaotian , Wang Jufeng , Wang Gang , Zhang Yanqiao , Fan Qingxia , Lu Chuangxin , Hu Changlu , Sun Meili , Wan Yiye , Sun Sanyuan , Wang Junye , Zhang Li , Shu Yongqian , Luo Jie , Zhu Dan , Shen Zhenwei , Yao Sheng , Shi Qingmei , Yang Jason , Shen Lin ,   GEMSTONE-303 Investigators, Xie Yanru , Lin Xiaoyan , Li Jiayi , Liu Yunpeng , Zhang Ruixing , Xiao Li , Chen Ping , Yang Xinhui , Wang Zishu , Luo Zhanxiong , Li Qi , Gao Yanrong , Wang Qi , Xiong Jianping , Fu Ting , Lin Yan , Xie Zhong , Zhao Yunbo , Mou Yiping , Zhang Tao , Liao Wangjun , Sun Yinping , Yan Dong , Ji Yanxia , Li Hongxia , Shi Yongquan , Pan Hongming , Deng Yanhong , Chen Yanhua , Yao Juntao , Hou Anji , Liang Xinjun 
Published: February 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;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