First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial

被引：15

作者：

Shen, Lin ^{[1
]}

Zhang, Yanqiao ^{[2
]}

Li, Ziyu ^{[3
]}

Zhang, Xiaotian ^{[1
]}

Gao, Xiangyu ^{[1
]}

Liu, Bo ^{[4
]}

Wang, Yusheng ^{[5
]}

Ba, Yi ^{[6
]}

Li, Ning ^{[7
]}

Zhang, Ruixing ^{[8
]}

Zhang, Jingdong ^{[9
]}

Chen, Ye ^{[10
]}

Chen, Jian ^{[11
]}

Huang, Mingzhu ^{[12
]}

Fu, Yang ^{[13
]}

Liu, Mulin ^{[14
]}

Liu, Zheng ^{[15
]}

Zhao, Jun ^{[16
]}

Li, Wei ^{[17
]}

Wei, Jia ^{[18
]}

Li, Changzheng ^{[4
]}

Xu, Nong ^{[19
]}

Guo, Zengqing ^{[20
]}

Cao, Bangwei ^{[21
]}

Liu, Lian ^{[22
]}

Nie, Peng ^{[23
]}

Wan, Lixin ^{[24
]}

Sheng, Lili ^{[25
]}

Liu, Zhenyang ^{[26
]}

He, Yifu ^{[27
]}

Gu, Kangsheng ^{[28
]}

Wu, Guowu ^{[29
]}

Wang, Weibo ^{[30
]}

Zhang, Futong ^{[31
]}

Qiu, Wensheng ^{[32
]}

Guo, Jun ^{[33
]}

Ying, Jieer ^{[34
]}

Pan, Hongming ^{[35
]}

Xu, Huiting ^{[36
]}

Yuan, Yuan ^{[37
]}

Bai, Yuansong ^{[38
]}

Wang, Zhenghua ^{[39
]}

Xu, Jiye ^{[40
]}

Zhao, Xuehong ^{[41
]}

Liu, Hao ^{[42
]}

Zhang, Xizhi ^{[43
]}

Dai, Wenxiang ^{[44
]}

Xu, Hongyan ^{[45
]}

Liu, Ming ^{[46
]}

Xie, Lin ^{[47
]}

机构：

[1] Peking Univ, State Key Lab Holist Integrat Management Gastroint, Beijing Key Lab Carcinogenesis & Translat Res, Canc Hosp & Inst, Beijing, Peoples R China

[2] Harbin Med Univ, Canc Hosp, Harbin, Peoples R China

[3] Peking Univ, Gastrointestinal Canc Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, Beijing, Peoples R China

[4] Shandong Canc Hosp, Dept Gastroenterol, Jinan, Peoples R China

[5] Shanxi Prov Canc Hosp, Taiyuan, Peoples R China

[6] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China

[7] Henan Canc Hosp, Zhengzhou, Peoples R China

[8] Hebei Med Univ, Hosp 4, Shijiazhuang, Peoples R China

[9] Liaoning Canc Hosp & Inst, Shenyang, Peoples R China

[10] Henan Univ Sci & Technol, Affiliated Hosp 1, Luoyang, Peoples R China

[11] Yantai Yuhuangding Hosp, Yantai, Peoples R China

[12] Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China

[13] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Peoples R China

[14] Bengbu Med Univ, Affiliated Hosp 1, Bengbu, Peoples R China

[15] HanDan Cent Hosp, Handan, Peoples R China

[16] Changzhi Peoples Hosp, Changzhi, Peoples R China

[17] Jilin Univ, Bethune Hosp 1, Changchun, Peoples R China

[18] Nanjing Drum Tower Hosp, Nanjing, Peoples R China

[19] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Hangzhou, Peoples R China

[20] Fujian Canc Hosp, Fuzhou, Peoples R China

[21] Capital Med Univ, Beijing Friendship Hosp, Beijing, Peoples R China

[22] Shandong Univ, Qilu Hosp, Jinan, Peoples R China

[23] Gansu Wuwei Tumour Hosp, Wuwei, Peoples R China

[24] Nanyang Cent Hosp, Nanyang, Peoples R China

[25] Wannan Med Coll, Affiliated Hosp 1, Wuhu, Peoples R China

[26] Hunan Canc Hosp, Changsha, Peoples R China

[27] Anhui Prov Canc Hosp, Hefei, Peoples R China

[28] Anhui Med Univ, Affiliated Hosp 1, Hefei, Peoples R China

[29] Meizhou Peoples Hosp, Meizhou, Peoples R China

[30] Shandong Prov Hosp, Jinan, Peoples R China

[31] Shijiazhuang Peoples Hosp, Shijiazhuang, Peoples R China

[32] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China

[33] Xingtai Peoples Hosp, Xingtai, Peoples R China

[34] Zhejiang Canc Hosp, Hangzhou, Peoples R China

[35] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China

[36] Hubei Canc Hosp, Wuhan, Peoples R China

[37] Xuzhou Cent Hosp, Xuzhou, Peoples R China

[38] Jilin Univ, Bethune Hosp 3, Changchun, Peoples R China

[39] Jinzhou Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China

[40] Zhoukou Cent Hosp, Zhoukou, Peoples R China

[41] Linfen Cent Hosp, Linfen, Peoples R China

[42] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China

[43] Northern Jiangsu Peoples Hosp, Yangzhou, Peoples R China

[44] Univ South China, Affiliated Hosp 1, Hengyang, Peoples R China

[45] Weihai Municipal Hosp, Weihai, Peoples R China

[46] Sichuan Univ, West China Hosp, Chengdu, Peoples R China

[47] Yunnan Canc Hosp, Kunming, Yunnan, Peoples R China

[48] Xinjiang Med Univ, Affiliated Canc Hosp, Urumqi, Peoples R China

[49] Taizhou Hosp Zhejiang Prov, Linhai, Peoples R China

[50] China Med Univ, Hosp 1, Shenyang, Peoples R China

来源：

NATURE MEDICINE | 2025年 / 31卷 / 04期

基金：

中国国家自然科学基金;

关键词：

OPEN-LABEL; IPILIMUMAB; CANCER; NIVOLUMAB; MULTICENTER; COMBINATION; CARBOPLATIN; PACLITAXEL; HER2;

D O I：

10.1038/s41591-024-03450-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here. This was a randomized, double-blind, placebo-controlled phase 3 study. Eligible patients were adults with untreated, unresectable, locally advanced or metastatic G/GEJ adenocarcinoma. Patients were randomized 1:1 to receive cadonilimab (10 mg kg(-1) every 3 weeks) or placebo plus chemotherapy (every 3 weeks). The primary endpoint was overall survival (OS) in the intention-to-treat population (one-sided significance level, P = 0.025). Secondary endpoints included OS in patients with a PD-L1 combined positive score >= 5, progression-free survival, objective response rate, duration of response and safety. As of 18 August 2023, 610 patients from 75 study centers were randomized to cadonilimab (n = 305) or placebo (n = 305). With a median follow-up of 18.7 months, the cadonilimab group had a significantly longer median OS (14.1 versus 11.1 months; hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.54-0.81; P < 0.001) than the placebo group. The primary endpoint was met. The median progression-free survival was 7.0 months versus 5.3 months (HR 0.53, 95% CI 0.44-0.65). The median OS in patients with a PD-L1 combined positive score >= 5 was 15.3 months versus 10.9 months (HR 0.58, 95% CI 0.41-0.82). The objective response rate was 65.2% versus 48.9% with a median duration of response of 8.8 months versus 4.4 months. Grade >= 3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group, and the most common were decreased platelet count, decreased neutrophil count and anemia. Most of the immune-related adverse events were grade 1 or 2. No new safety signals were observed. Cadonilimab plus chemotherapy significantly improved OS with a manageable safety profile in patients with advanced G/GEJ adenocarcinoma.

引用

页码：1368 / 1368

页数：23

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