NCT07480954

Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16)

A Phase 1/2, Open-Label, Biomarker-Assigned Study of Dual-Targeting CAR-NK Cells Directed Against Mesothelin (MSLN), Folate Receptor Alpha (FRα/FOLR1), and/or MUC16 (CA125) in Patients With Recurrent or Refractory High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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 description

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 lymphodepleting chemotherapy (cyclophosphamide and fludarabine) followed by CAR-NK administration. In this example, CAR-NK cells are given intraperitoneally via an implanted port to maximize exposure to peritoneal disease, with optional intravenous dosing per investigator judgment. Participants are monitored closely for cytokine release syndrome (CRS), neurotoxicity (ICANS), cytopenias, infections, and other adverse events. Response assessments are performed by RECIST v1.1 at regular intervals, with CA 125 trends collected as supportive disease activity data. Follow-up: Participants are followed for adverse events through 12 months and for survival for up to 24 months. Long-term follow-up for gene-modified cell therapy safety may be required per local regulations.

Conditions

• Epithelial Ovarian Cancer
• Primary Peritoneal Carcinoma
• Fallopian Tube Carcinoma
• Recurrent or Refractory Disease After Standard Therapies

Interventions

Type	Name	Description
BIOLOGICAL	Dual-target CAR-NK cell product	(Arm-specific)
DRUG	Lymphodepleting chemotherapy	(cyclophosphamide and fludarabine)
OTHER	Standard supportive care	antimicrobial prophylaxis per institutional practice

Timeline

• Start date: 2026-02-04
• Primary completion: 2027-02-17
• Completion: 2028-05-17
• First posted: 2026-03-18
• Last updated: 2026-03-18

Locations

1 site across 1 country: China