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.

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.

Inclusion Criteria:

• Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (high-grade serous preferred).
• Recurrent or refractory disease after at least 2 prior systemic treatment lines (including a platinum-based regimen unless contraindicated).
• Measurable disease per RECIST v1.1.
• Tumor expresses at least two of the following targets above protocol-defined threshold: MSLN, FRalpha (FOLR1), MUC16 (CA 125) (archival or fresh biopsy).
• ECOG performance status 0-1.
• Adequate organ function (example): ANC >= 1.0 x 10^9/L; platelets >= 75 x 10^9/L; hemoglobin >= 8 g/dL; AST/ALT <= 3 x ULN (<= 5 x ULN with liver metastases); total bilirubin <= 1.5 x ULN; creatinine clearance >= 50 mL/min.
• Negative pregnancy test for women of childbearing potential; agreement to use effective contraception through 12 months post-infusion (or per local gene-therapy guidance).
• Able to comply with study procedures and follow-up schedule; written informed consent.

Exclusion Criteria:

• Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 6 months (or any prior therapy directed to the same target, per protocol).
• Active central nervous system (CNS) metastases or carcinomatous meningitis requiring therapy.
• Uncontrolled infection, including active tuberculosis; or clinically significant, uncontrolled viral infection.
• Known HIV infection with uncontrolled viremia; active hepatitis B or hepatitis C with detectable viral load (testing required at screening).
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, NYHA Class III/IV heart failure).
• Active autoimmune disease requiring systemic immunosuppression within 30 days (physiologic steroid replacement allowed).
• Concurrent anti-cancer therapy (chemotherapy, targeted therapy, radiotherapy) not permitted within a protocol-defined washout period.
• Major surgery within 4 weeks prior to lymphodepletion (except minor procedures).

Female