Hypoxia-responsive CEA CAR-T cells therapy for relapsed or refractory non-small cell lung cancer: A single-arm, open-label, phase I trial.

作者：Shuang Wei, Jiaqi Guo, Xueli Bai, Cheng Qian, Yicheng Zhang, Ling Zhou, Weiwei Tian, Xiansheng Liu, Jia Wei · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.8517 · 被引用次数：6 · 研究领域：CAR-T cell therapy research

8517 Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in targeted tumor cells eradication. However, data on CAR-T therapies in NSCLC remain limited. This study evaluates the safety and efficacy of CEA CAR-T cell therapy in r/r NSCLC. Methods: Adult metastatic NSCLC patients with relapse after ≥2 lines of treatment were enrolled and administered intravenous CEA CAR-T cells at three dose levels (0.75×10 6 , 1.5×10 6 , and 3×10 6 CEA CAR-T cells/kg).Peripheral blood samples were collected on day 28 post-infusion and analyzed using 10x Genomics single-cell RNA sequencing (scRNA-seq).The primary endpoint was safety , and secondary endpoints including efficacy and pharmacological evaluation. Results: From August 1, 2023, to July 15, 2024, a total of 18 patients were screened, and 15 received CAR-T infusion. The median age was 60 years , with a median of 4 prior therapy lines (range 2-10 lines). Among 6 patients receiving the maximum dose (3×10 6 cells/kg), no dose-limiting toxicities, grade 4 cytokine release syndrome or ICANS were observed. No adverse events were observed during a three-month long-term safety evaluation. With a median follow-up of 5.7 months, 7 patients achieved PR, 6 had SD, and 2 experienced PD. The best DCR was 87%, and ORR was 47%. Notably, patients with ≥30% intense and complete CEA staining in tumor cells and no brain metast...