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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03037-z

摘要内容如下：

Claudin18.2（CLDN18.2）随着多种恶性肿瘤尤其是胃肠道肿瘤的发展而高表达，并逐渐成为肿瘤治疗的新靶点。Satricabtagene Autoleucel（SATRI-CEL）/CT041是一种靶向CLDN18.2的自体嵌合抗原受体（CAR）T细胞，CT041-CG4006试验的中期结果于2022年6月报道。在此，我们介绍了这项单臂、开放标签、1期试验的最终结果，该试验评估了SATRI-CEL在CLDN18.2阳性晚期胃肠道癌患者中的安全性和有效性。该试验包括4个不同队列的剂量递增阶段（n=15）和剂量扩大阶段（总n=83）：队列1，61例标准化疗难治性胃肠道癌患者接受SATRI-CEL单药治疗；队列2，SATRI-CEL联合抗PD-1治疗15例标准化疗难治性胃肠癌患者；队列3，SATRI-CEL作为5例胃肠道肿瘤患者一线治疗后的序贯治疗；队列4，SATRI-CEL单药治疗2例抗CLDN18.2单克隆抗体难治性胃癌患者。主要终点是安全性；次要终点包括疗效、药代动力学和免疫原性。共有98名患者接受了Satri-Cel输注，其中89名患者的剂量为2.5×108，6名患者的剂量为3.75×108，3名患者的剂量为5.0×108。单采后中位随访时间为32.4个月（95%可信区间（CI）:27.3，36.5）。未报告剂量限制性毒性、治疗相关死亡或免疫效应细胞相关神经毒性综合征。96.9%的患者出现细胞因子释放综合征，均为1-2级。8例（8.2%）患者出现胃黏膜损伤。98例患者的总缓解率和疾病控制率分别为38.8%和91.8%，中位无进展生存期和总生存期分别为4.4个月（95%CI:3.7，6.6）和8.8个月（95%CI:7.1，10.2）。SATRI-CEL在CLDN18.2阳性晚期胃肠癌患者中显示出治疗潜力，且安全性可控。ClinicalTrials.gov标识符：NCT03874897。

英文原文如下：

Abstracts

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 108, six with 3.75 × 108 and three with 5.0 × 108 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

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