Phase 1/2 Study of Dual-Target CAR-NK Cells in Recurrent Ovarian Cancer

Status: RECRUITING | Phase: PHASE1/PHASE2 Condition(s): Epithelial Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Carcinoma, Recurrent or Refractory Disease After Standard Therapies Intervention(s): Dual-target CAR-NK cell product (BIOLOGICAL), Lymphodepleting chemotherapy (DRUG), Standard supportive care (OTHER) This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in participants with recurrent or refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer. At screening, each participant's tumor is assessed for expression of Mesothelin (MSLN), Folate Receptor alpha (FRalpha/FOLR1), and MUC16 (CA 125). Participants are assigned to the dual-target CAR-NK product that best matches their tumor antigen profile to reduce the risk of antigen escape. Detailed: The study has two parts: (1) dose escalation using a standard 3+3 design within each antigen-pair cohort to determine safety and a recommended Phase 2 dose (RP2D), and (2) dose expansion at the RP2D to explore preliminary efficacy and translational biomarkers. Target selection (biomarker assignment): Tumor tissue (archival or fresh biopsy) is evaluated by immunohistochemistry (IHC) and/or flow cytometry for MSLN, FRalpha, and MUC16. Eligibility requires expression of at least two of the three targets above a pre-specified threshold. If all three are positive, a Target Selection Committee assigns the participant to the dual-target pair with the highest combined expression (e.g., H-score or percent positive cells) and acceptable normal-tissue risk. Treatment schema: Participants receive lym Primary Outcome(s): Incidence of dose-limiting toxicities (DLTs); Incidence and severity of treatment-emergent adverse events Enrollment: 36 (ESTIMATED) Lead Sponsor: Beijing Biotech Start: 2026-02-04 | Primary Completion: 2027-02-17