CT041是一种嵌合抗原受体（CAR）修饰的T细胞疗法，专门针对实体瘤中的claudin18.2。在此，我们报告了两项探索性临床试验的汇总分析结果，以评估 CT041 在既往治疗过的胰腺癌 (PC) 患者中的作用。这两项多中心、开放标签 I/Ib 期试验（CT041-CG4006、CT041-ST-01）有类似的目标人群和评估时间表。主要目标是评估 CT041 的安全性和耐受性，次要目标包括疗效、药代动力学和免疫原性。合并队列由 24 名晚期 PC 患者组成。其中，5名患者（20.8%）之前接受过一种治疗，而19名患者（79.2%）接受过≥2种治疗。最常见的 3 级或以上治疗中出现的不良事件是预处理相关的血液学毒性。细胞因子释放综合征 (CRS) 和胃肠道疾病是报告最多的 1 级或 2 级不良事件。总体有效率和疾病控制率分别为16.7%和70.8%。输注后中位无进展生存期（mPFS）为3.3个月（95% CI，1.8至6.2），中位总生存期（mOS）为10.0个月（95% CI，5.5至17.6）。中位缓解持续时间 (mDoR) 为 9.5 个月（95% CI，2.6 至未达到），12 个月时的 DoR 率为 50%（95% CI，5.8 至 84.5）。与疾病进展组相比，实现部分缓解/疾病稳定的患者的 mPFS（6.0 vs 1.0 个月，P < .001）和 mOS（17.6 vs 4.0 个月，P < .001）延长。 17 名 (70.8%) 患者的 CA19-9 水平降低了至少 30%。在先前治疗进展后的转移性 PC 患者中，CT041 显示出可耐受的安全性和令人鼓舞的抗癌功效信号。这里观察到的响应效益需要在未来确定。

CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC).These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity.The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients.In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.