Sugemalimab一线联合化疗治疗晚期癌症，这一成果由北京大学肿瘤医院林申研究团队经过不懈努力而取得。该项研究成果发表在2025年2月24日出版的《美国医学会杂志》上。

重要性:胃癌，包括胃食管结癌，是世界上最常见的癌症之一，死亡率很高。Sugemalimab是一种全人源性抗程序性死亡配体1 （PD-L1）抗体。在一项1b期研究中，sugemalimab联合化疗在未接受治疗、不可切除、局部晚期或转移性胃或胃食管交界处腺癌患者中显示出良好的抗肿瘤活性和安全性。在GEMSTONE-303 3期试验中进一步评估了该组合。

目的:与安慰剂加CAPOX相比，sugemalimab联合卡培他滨和奥沙利铂（CAPOX）作为一线治疗PD-L1联合阳性评分（CPS）大于等于5的不可切除的局部晚期或转移性胃或胃食管交界腺癌患者的疗效。

设计、设置和参与者：GEMSTONE 303是一项3期、随机、双盲、安慰剂对照研究，于2019年4月9日至2021年12月29日在中国54个地点进行，随访至2023年7月9日。共有479例符合条件的局部晚期或转移性胃或胃食管交界处腺癌患者，PD-L1 CPS为5或更高，既往未接受任何全身治疗。患者每3周接受一次sugemalimab （1200mg静脉注射）（n= 241）或安慰剂（n= 238）治疗，持续24个月，每3周加加CAPOX治疗，持续6个周期。

主要成果和措施：主要结局是总生存期和研究者评估的无进展生存期。

结果:两组患者的基线特征平衡良好。大多数患者为男性（sugemalimab组为71.4%，安慰剂组为74.8%）。舒吉马利单抗组中位随访时间为25.1个月，安慰剂组中位随访时间为26.3个月。sugemalimab组在总生存期(中位，15.6个月vs 12.6个月；风险比，0.75；P = 0.006)和无进展生存期(中位，7.6个月vs 6.1个月；风险比0.66；P & lt; 措施)。3级或以上的治疗相关不良事件发生在53.9%的苏美马利单抗组和50.6%的安慰剂组患者中。

研究结果表明，Sugemalimab联合化疗显著延长了先前未经治疗的不可切除的局部晚期或转移性胃或胃食管交界腺癌患者的总生存期和无进展生存期，安全性可管理。

附：英文原文

Title: First-Line Sugemalimab Plus Chemotherapy for Advanced Gastric Cancer: The GEMSTONE-303 Randomized Clinical Trial

Author: 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, GEMSTONE- Investigators, 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

Issue&Volume: 2025-02-24

Abstract: 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<.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.

DOI: 10.1001/jama.2024.28463

Source: https://jamanetwork.com/journals/jama/fullarticle/2830739