Dual-Target CAR-NK Cells in Recurrent or Refractory Epithelial Ovarian Cancer

EB-DUALNK is an investigational, genetically engineered NK-cell product designed to recognize tumor cells through two surface antigens. Dual targeting is intended to reduce antigen-escape and improve tumor recognition in heterogeneous solid tumors. Prior to first patient dosing, a biomarker assessment will review ovarian tumor expression patterns for GD2, MUC1, PSMA, and mesothelin (using immunohistochemistry and/or flow cytometry where feasible). The final dual-target pair will be chosen based on a pre-specified decision framework (antigen prevalence, co-expression, safety rationale, and manufacturing feasibility). The study includes a Phase 1 dose-escalation portion to identify the recommended Phase 2 dose (RP2D) and a Phase 2 expansion portion to further characterize safety and estimate preliminary efficacy at the RP2D.

Participants will receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) followed by a single infusion of EB-DUALNK. Repeat dosing may be permitted in selected cohorts if protocol-defined safety criteria are met. Safety monitoring includes assessment of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, infections, and organ toxicities. Efficacy assessments include radiographic response by RECIST v1.1 and CA-125 (where applicable). Correlative studies evaluate CAR-NK persistence, phenotype, cytokines, and relationships between antigen expression and clinical outcomes.

Inclusion criteria

• Age 18-75 years; able to provide written informed consent.
• Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma that is recurrent or refractory after standard therapy (at least 2 prior systemic regimens), with measurable disease per RECIST v1.1 and ECOG performance status 0-1.
• Tumor tissue available for antigen assessment. Participant must meet protocol-defined positivity for the selected dual-target pair (example: 1 target expressed in >=50% of tumor cells by IHC and the second target in >=20%).
• Adequate organ function per protocol-specified labs; negative pregnancy test nd agrees to use effective contraception for a protocol-defined period after infusion.

Exclusion criteria

• Active CNS metastases or carcinomatous meningitis (unless treated and stable for a protocol-defined period).
• Prior gene-modified cell therapy targeting any of the study antigens (GD2, MUC1, PSMA, mesothelin) within 6 months.
• Uncontrolled active infection (including uncontrolled HIV, HBV, or HCV) or active systemic fungal infection.
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina, uncontrolled arrhythmia) or LVEF <50% .
• Active autoimmune disease requiring systemic immunosuppression within 14 days prior to lymphodepletion (physiologic steroid replacement permitted).
• History of organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Pregnant or breastfeeding.
• Any condition that, in the investigator's judgment, would compromise participant safety or compliance.