Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results
Changsong Qi, Jifang Gong, Jian Li, Dan Liu, Yanru Qin, Sai Ge, Miao Zhang, Zhi Peng, Jun Zhou, Yanshuo Cao, Xiaotian Zhang, Zhihao Lu, Ming Lu, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Xiaohui Peng, Huiping Gao, Zhen Liu, Huamao Wang, Daijing Yuan, Jun Xiao, Hong Ma, Wei Wang, Zonghai Li, Lin Shen, Changsong Qi, Jifang Gong, Jian Li, Dan Liu, Yanru Qin, Sai Ge, Miao Zhang, Zhi Peng, Jun Zhou, Yanshuo Cao, Xiaotian Zhang, Zhihao Lu, Ming Lu, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Xiaohui Peng, Huiping Gao, Zhen Liu, Huamao Wang, Daijing Yuan, Jun Xiao, Hong Ma, Wei Wang, Zonghai Li, Lin Shen
Abstract
Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 108, 3.75 × 108 or 5.0 × 108 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.
Conflict of interest statement
The authors declare no competing interests.
© 2022. The Author(s).
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