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Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Qi Changsong[1] * ; Liu Chang[2] * ; Peng Zhi[3] * ; Zhang Yanqiao[4] * ; Wei Jia[5] * ; Qiu Wensheng[6] * ; Zhang Xiaotian[3] ; Pan Hongming[7] ; Niu Zuoxing[8] ; Qiu Meng[9] ; Qin Yanru[10] ; Fang Weijia[11] ; Ye Feng[12] ; Li Ning[13] ; Liu Tianshu[14] ; Liu Anwen[15] ; Zhang Xizhi[16] ; Hu Changlu[17] ; Zhang Jun[18] ; Cui Jiuwei[19] ; Lin Xiaoyan[20] ; Wang Shubin[21] ; Zhang Jian[22] ; Lin Tongyu[23] ; Qu Xiujuan[24] ; Yuan Xianglin[25] ; Gong Jifang[3] ; Li Jian[3] ; Gao Wanwan[26] ; Gai Lun[26] ; Wang Yumeng[26] ; Yuan Daijing[26] ; Li Zonghai[26] ; Shen Lin[27] ;
机构： [1]Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. [2]Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. [3]Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. [4]Harbin Medical University Cancer Hospital, Harbin, China. [5]Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. [6]The Affiliated Hospital of Qingdao University, Qingdao, China. [7]Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [8]Cancer Hospital of Shandong First Medical University, Jinan, China. [9]West China Hospital, Sichuan University, Colorectal Cancer Center, Chengdu, China. [10]The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [11]Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [12]Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. [13]Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. [14]Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. [15]The Second Affiliated Hospital of Nanchang University, Nanchang, China. [16]Northern Jiangsu People's Hospital, Yangzhou, China. [17]Anhui Provincial Cancer Hospital, Hefei, China. [18]Department of Oncology, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [19]The First Hospital of Jilin University, Changchun, China. [20]Fujian Medical University Union Hospital, Fuzhou, China. [21]Peking University Shenzhen Hospital, Shenzhen, China. [22]Fudan University Shanghai Cancer Center, Shanghai, China. [23]Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China. [24]The First Hospital of China Medical University, Shenyang, China. [25]Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [26]CARsgen Therapeutics, Shanghai, China. [27]Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
出处：
DOI： 10.1016/S0140-6736(25)00860-8
ISSN：

摘要：
Claudin-18 isoform 2 (CLDN18.2) has emerged as a promising therapeutic target in gastric or gastro-oesophageal junction cancer. Satricabtagene autoleucel (satri-cel; also known as CT041), an autologous CLDN18.2-specific chimeric antigen receptor (CAR) T-cell therapy, showed encouraging activity in previously treated patients with advanced gastric or gastro-oesophageal junction cancer in phase 1 clinical trials. In this Article, we report the primary results from the phase 2 pivotal trial (CT041-ST-01) investigating the efficacy and safety of satri-cel for gastric or gastro-oesophageal junction cancer.In this open-label, multicentre, randomised controlled trial conducted in China, patients with CLDN18.2-positive (immunohistochemistry expression intensity ≥2+ and positive tumour cells ≥40%) advanced gastric or gastro-oesophageal junction cancer, who were refractory to at least two previous lines of treatment, were randomly allocated (2:1) to receive satri-cel or treatment of physician's choice (TPC). In the satri-cel group, satri-cel was infused up to three times at a dose of 250 × 106 cells. For the TPC group, one of the standard-of-care drugs (nivolumab, paclitaxel, docetaxel, irinotecan, or rivoceranib [apatinib]) was given, per the physician's decision. Those who had disease progression or drug intolerance in the TPC group could receive subsequent satri-cel, if eligible. The primary endpoint was progression-free survival, assessed by an independent review committee, in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04581473), and is closed to new patients.Between March 22, 2022, and July 29, 2024, 266 patients were screened, of whom 156 were randomly allocated to the satri-cel group (n=104) or TPC group (n=52). 88 (85%) patients in the satri-cel group and 48 (92%) patients in the TPC group received study drug. In the satri-cel group, 28 (27%) patients had previously received three or more lines of treatment and 72 (69%) patients had peritoneal metastasis. In the TPC group, ten (19%) patients had previously received three or more lines of treatment and 31 (60%) patients had peritoneal metastasis. The median follow-up time for progression-free survival was 9·07 months (95% CI 6·21-13·01) in the satri-cel group and 3·45 months (2·89-not estimable) in the TPC group, based on the reverse Kaplan-Meier method. In the intention-to-treat population, median progression-free survival was 3·25 months (95% CI 2·86-4·53) in the satri-cel group and 1·77 months (1·61-2·04) in the TPC group (hazard ratio 0·37 [95% CI 0·24-0·56]; one-sided log-rank p<0·0001). In the safety analysis set (all patients who received at least one dose of study drug), grade 3 or higher treatment-emergent adverse events occurred in 87 (99%) of 88 patients in the satri-cel group and 30 (63%) of 48 patients in the TPC group. The most common grade 3 or worse treatment-emergent adverse events related to treatment were decreased lymphocyte count (86 [98%] of 88 patients), decreased white blood cell count (68 [77%] patients), and decreased neutrophil count (58 [66%] patients) in the satri-cel group. Cytokine release syndrome occurred in 84 (95%) of 88 patients in the satri-cel group.This is the first randomised controlled trial of CAR T-cell therapy in solid tumours globally. Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile. These results support satri-cel as a new third-line treatment for advanced gastric or gastro-oesophageal junction cancer patients.CARsgen Therapeutics.Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

基金：
This study was funded by CARsgen Therapeutics, the National Key Research and Development Program of China (2022YFC2505006), the National Natural Science Foundation of China (U22A20327), Beijing Hospitals Authority Youth Programme (QMS20201101), Science Foundation of Peking University Cancer Hospital (JC202406), Clinical Medicine Plus X-Young Scholars Project of Peking University, and the Peking University Clinical Scientist Training Program.
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出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：内科
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：内科
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出版当年[2024]版：
Q1 MEDICINE, GENERAL & INTERNAL
最新[2024]版：
Q1 MEDICINE, GENERAL & INTERNAL

影响因子： 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

第一作者：
第一作者机构： [1]Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China.
共同第一作者：
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推荐引用方式(GB/T 7714)：
Qi Changsong,Liu Chang,Peng Zhi,et al.Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial[J].Lancet (London, England).2025,405(10494):2049-2060.doi:10.1016/S0140-6736(25)00860-8.
APA：
Qi Changsong,Liu Chang,Peng Zhi,Zhang Yanqiao,Wei Jia...&Shen Lin.(2025).Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial.Lancet (London, England),405,(10494)
MLA：
Qi Changsong,et al."Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial".Lancet (London, England) 405..10494(2025):2049-2060

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