Phase 12 Study of Dual-Target CAR-NK Cell Therapy for Adults With Relapsed or Refractory Small Cell Lung Cancer

What this Trial Is About

Researchers are evaluating the safety, feasibility, and early antitumor effects of allogeneic dual-target CAR-NK cell products in adults with relapsed or refractory small cell lung cancer SCLC. This open-label, multi-center Phase 12 trial focuses on three off-the-shelf CAR-NK therapies designed to target combinations of DLL3, CD56, and GD2 proteins commonly found on SCLC tumors. The study aims to identify the most promising dual-target CAR-NK construct to proceed to further testing. Participants will undergo screening including tumor antigen profiling to confirm target presence. The trial includes a Phase 1 dose escalation with up to three parallel arms, each testing a different CAR-NK dual-target combination DLL3CD56, DLL3GD2, CD56GD2. After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, participants receive CAR-NK infusions, possibly repeated within a cycle or given in a second cycle for responders. A pre-planned interim review will select the best construct for a Phase 2 expansion cohort at the recommended dose. During the study, participants will be closely monitored for safety issues such as cytokine release syndrome and neurotoxicity, with assessments of dose-limiting toxicities and maximum tolerated dose over 12 months. Clinical follow-up for efficacy and late side effects continues for 24 months, with potential long-term monitoring for up to 15 years to watch for delayed adverse events. Researchers will evaluate tumor response, progression-free survival, and overall survival as key outcomes.

Adaptive Phase 1/2 Study of Dual-Target CAR-NK Cells in Relapsed/Refractory Small Cell Lung Cancer (SCLC)