Phase 12 Study of Dual-Target CAR-NK Cell Therapy for Adults with Advanced or Metastatic Colorectal Cancer Targeting CEA, GUCY2C, and HER2 Antigens

What this Trial Is About

Researchers are evaluating the safety, tolerability, and early anti-tumor activity of a new dual-target chimeric antigen receptor natural killer CAR-NK cell therapy in adults with advanced or metastatic colorectal cancer. This Phase 12 study focuses on patients whose tumors express specific antigen pairs, aiming to improve tumor targeting and reduce escape by using combinations of CEA, GUCY2C, and HER2 markers. The study explores this innovative approach as a potentially safer, off-the-shelf cellular therapy with less risk of severe immune reactions than similar treatments. Participants are assigned to one of three groups based on tumor antigen co-expression CEAGUCY2C, CEAHER2, or GUCY2CHER2. They receive lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide before infusion with the assigned dual-target CAR-NK cells. Some participants may receive a second infusion in the same treatment cycle if safety allows. After an initial dose escalation phase, the safest and most effective target pair will be chosen for further study expansion. Throughout the study, participants will be closely monitored in the hospital during the early post-infusion period. Researchers will assess dose-limiting toxicities, maximum tolerated dose, and tumor response over 12 weeks, along with longer-term safety and disease control for up to 24 months. Tumor tissue will undergo biomarker testing to confirm eligibility and monitor treatment effects. Participation includes regular clinical evaluations, laboratory tests, and imaging to track treatment impact and safety over time.

Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer