Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Early Drug Development Center, Peking University Cancer Hospital and Institute, Beijing, China.
Nat Med. 2022 Jun;28(6):1189-1198. doi: 10.1038/s41591-022-01800-8. Epub 2022 May 9.
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 × 10, 3.75 × 10 or 5.0 × 10 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.
尽管在血液恶性肿瘤方面取得了成功，但嵌合抗原受体 (CAR) T 细胞疗法治疗实体瘤的治疗领域仍然有限。 Claudin18.2 (CLDN18.2) 导向的 CAR T 细胞在一项临床前研究中显示出对胃癌 (GC) 的有希望的疗效。 在这里，我们报告了一项正在进行的、开放标签、单臂、I 期临床试验的中期分析结果，该试验评估了 CLDN18.2 靶向 CAR T 细胞 (CT041) 在先前治疗过的 CLDN18.2 阳性消化系统癌症患者中的疗效 (NCT03874897)。 主要目的是 CT041 输注后的安全性；次要目标包括 CT041 的疗效、药代动力学和免疫原性。 我们用三种 CT041 剂量之一治疗了 37 例患者：2.5×10、3.75×10 或 5.0×10 个细胞。 所有患者均经历了 3 级或更高的血液学毒性。 94.6%的患者发生了 1 级或 2 级细胞因子释放综合征 (CRS)。 未报告 3 级或更高 CRS 或神经毒性、治疗相关死亡或剂量限制性毒性。 总缓解率 (ORR) 和疾病控制率 (DCR) 分别达到 48.6%和 73.0%。 6 个月的缓解率为 44.8%。 在 GC 患者中，ORR 和 DCR 分别达到 57.1%和 75.0%，6 个月的总生存率为 81.2%。 这些初步结果表明，CT041 在接受过大量预处理的 CLDN18.2 阳性消化系统癌症患者中具有良好的疗效和可接受的安全性，特别是在 GC 患者中。
