Phase 12 Study of Allogeneic Dual-target CLDN18.2HER2 CAR-NK Cell Therapy with Fludarabine and Cyclophosphamide in Adults with Advanced Gastric or Gastroesophageal Junction Cancer

What this Trial Is About

Researchers are evaluating a new cell therapy combining allogeneic CAR-NK cells targeting both CLDN18.2 and HER2 ERBB2 in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have previously undergone standard treatments. This phase 12 study aims to find the best dose and assess early signs of antitumor activity while exploring how tumor markers relate to treatment outcomes. The approach addresses the variability in cancer cell targets by combining two specific antigens relevant to this disease. In the phase 1 part, participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide from days -5 to -3, followed by three intravenous infusions of the CAR-NK cells on days 0, 3, and 7. The study uses a 33 dose-escalation design to identify dose-limiting toxicities and the maximum tolerated dose. In phase 2, patients receive the recommended dose on the same schedule, focusing on CLDN18.2-positive cancers, with HER2 status evaluated for subgroup analyses. Participants will be closely monitored through safety evaluations and tumor response assessments over several months, including tracking objective response rates, progression-free survival, and overall survival. The study also measures how the CAR-NK cells expand and persist in the body. Biomarker studies will help understand the link between antigen expression and clinical outcomes. The total study duration includes follow-ups up to 24 months to evaluate treatment effects and safety profiles.

Dual-target CLDN18.2/HER2 CAR-NK Cells for Advanced Gastric/GEJ Cancer