Phase 1 Study of Dual-Target Nectin-4HER2 CAR-NK Cell Therapy with Fludarabine and Cyclophosphamide in Adults With Advanced or Metastatic Urothelial Carcinoma

What this Trial Is About

Researchers are studying an allogeneic dual-target Nectin-4HER2 CAR-NK cell therapy in adults with relapsed or refractory locally advanced or metastatic urothelial carcinoma. This phase 1, open-label study aims to evaluate the safety, feasibility, and preliminary anti-tumor activity of this investigational treatment following prior standard therapies including platinum-based chemotherapy and PD-1PD-L1 inhibitors. The therapy targets two antigens to improve tumor coverage and reduce treatment escape, addressing the high unmet needs in advanced urothelial cancer. The investigational product is an allogeneic cord-blood-derived CAR-NK cell therapy engineered to recognize both Nectin-4 and HER2 antigens, with an inducible safety switch. Patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before intravenous infusions of the CAR-NK cells on Day 1 and Day 8 of each 21-day cycle. The study includes a dose-escalation phase to find the maximum tolerated dose or recommended dose followed by a dose-expansion phase to further assess safety and early efficacy. Participants undergo tumor assessments using RECIST v1.1 criteria for measurable disease and are closely monitored for side effects such as cytokine release syndrome, neurotoxicity, graft-versus-host disease, and infusion reactions. Additional evaluations include biomarker analyses and cardiopulmonary monitoring. The primary outcomes focus on dose-limiting toxicities and adverse event severity over 12 months, with secondary outcomes assessing response rates, disease control, and survival over up to 24 months. The study expects participant involvement over this period with regular safety and efficacy assessments.

Dual-Target Nectin-4/HER2 CAR-NK Cells in Advanced Urothelial Carcinoma