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

Key Takeaway
Consider dual-target CAR-NK cells for recurrent ovarian cancer in ongoing trials.

This ongoing Phase 1/2 study investigates the safety, tolerability, and preliminary anti-tumor activity of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in patients with recurrent or refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer. The study employs a 3+3 dose escalation design to establish a recommended Phase 2 dose (RP2D) for each antigen-pair cohort, followed by dose expansion to evaluate efficacy and biomarkers. Tumor expression of Mesothelin (MSLN), Folate Receptor alpha (FRalpha), and MUC16 is assessed via immunohistochemistry or flow cytometry, with eligibility requiring expression of at least two targets. Participants are assigned to a dual-target CAR-NK product based on their tumor antigen profile to minimize antigen escape. The primary outcomes include the incidence of dose-limiting toxicities and treatment-emergent adverse events. The study aims to enroll 36 participants, with completion anticipated in 2027. Safety and efficacy data will inform future trials and potential therapeutic strategies for these challenging malignancies.

AI Accuracy Review: 9/10 · Auto-published
View Original Abstract ↓
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
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