CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

The trial progresses through sequential Phase Ia (dose-finding) and Phase Ib (dose-expansion) stages. Phase Ia cessation triggers include either confirmation of Recommended Phase II Dose (RP2D) or investigator-verified favorable therapeutic index at any dose level. Post-Phase Ia completion, protocol amendment submission to the Institutional Review Board precedes Phase Ib initiation, featuring multi-cohort expansion (n=9-18/cohort) across specified malignancies: colorectal adenocarcinoma (CRC), gastric carcinoma (GC), high-grade serous ovarian carcinoma (HGSOC), breast cancer (BC), non-small cell lung cancer (NSCLC), SCLC, metastatic castration-resistant prostate cancer (mCRPC), clear cell renal cell carcinoma (ccRCC), and cervical squamous cell carcinoma (CSCC), etc. This is a single-center, open-label, dose-escalation study consisting of two distinct treatment cohorts for patients with CDH17-positive advanced malignant solid tumors: Cohort 1 (CDH17 CART): A dose-escalating (3+3 design) study with 3 dose levels: 1.0×10\^6, 3.0×10\^6, and 6.0×10\^6 CAR+ cells/kg. Cohort 2 (FAST LACO-Stim CDH17 CART): A dose-escalating (3+3 design) study with 2 dose levels: 3.0×10\^4, and 1.0×10\^5 CAR+ cells/kg. During dose escalation, the investigator may adjust the dose level as appropriate based on the accumulated human safety and tolerability, pharmacokinetic, and pharmacodynamic data. The final sample size will depend on the occurrence of dose-limiting toxicities (DLTs), the number of dose escalation groups before observing DLTs, and the maximum tolerated dose (MTD). The observation period for dose-limiting toxicity (DLT) is set from the start of cell infusion to 4 weeks after the completion of cell infusion (D0 to D28).