Phase 12 Adaptive 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 preliminary anti-tumor 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, adaptive Phase 12 trial addresses the challenges of rapid progression and antigen heterogeneity in SCLC by testing three dual-target CAR-NK constructs aimed at reducing the risk of tumor escape. The study involves selecting the most suitable construct for further evaluation based on safety and early activity. Participants receive lymphodepleting chemotherapy followed by infusions of one of three off-the-shelf dual-target CAR-NK cell products engineered from healthy donor cells, each designed to target specific tumor antigens and include safety and persistence features. During Phase 1, dose escalation assesses three parallel arms, each with a different dual-target CAR-NK construct, to find the maximum tolerated dose MTD and recommended Phase 2 dose RP2D. An interim review selects the best construct for Phase 2 expansion to further characterize safety and anti-tumor activity. Repeat dosing and additional cycles are allowed based on response and safety. Participants undergo screening including tumor antigen profiling and biomarker assessments before treatment. Safety is closely monitored for cytokine release syndrome, neurotoxicity, infections, and other adverse events, with oversight by an independent committee. Follow-up includes clinical monitoring for 24 months to assess effectiveness and late side effects, with the possibility of extended long-term follow-up for up to 15 years as required by regulations. The primary outcomes focus on dose-limiting toxicities and maximum tolerated dose within 12 months.

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