CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

The investigational product used in this study, UCLH801 cells, is a CAR-T cell therapy specifically targeting CDH17. The proposed indication includes CDH17-positive advanced solid tumors, such as but not limited to colorectal cancer, gastric cancer, pancreatic cancer, biliary tract tumors, neuroendocrine tumors, ovarian cancer, and lung cancer. The primary objective of this study is to evaluate the safety and tolerability of UCLH801 cells in patients with CDH17-positive advanced malignant solid tumors. The secondary objectives include assessing the preliminary efficacy of UCLH801 cells, their pharmacokinetics and pharmacodynamics in the body, and their immunogenicity. This study aims to observe how the infusion of UCLH801 cells affects patients 's body, including any discomfort or changes in laboratory test results. Additionally, it will evaluate whether UCLH801 cells have any effect on tumor. Furthermore, the study will investigate how UCLH801 cells are metabolized; the mechanisms through which they exert their effects, and how to develops any immune response or rejection against UCLH801 cells.

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 study has 3 dose levels and follows a "3+3 design," with an estimated enrollment of 9 to 18 subjects. 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). Considering the possibility of cell production preparation failure or other reasons (such as rapid disease progression during cell preparation) leading to subjects ultimately being unable to receive cell infusion therapy, the number of participants in the cell collection and preparation process may be greater than the planned number of cases. 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). The starting dose of cell infusion therapy in this clinical study is set at 1.0×10\^6/Kg, and the maximum dose is set at 6.0×10\^6/Kg.