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This study evaluates the safety, tolerability, and preliminary anti-tumor activity of EB-DUALNK, a dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy, in adults with recurrent or refractory epithelial ovarian cancer. Candidates for targeting include GD2, MUC1, PSMA, and mesothelin. After baseline biomarker assessment (tumor antigen expression), the program will select the most suitable dual-target pair for clinical testing. Participants will receive lymphodepleting chemotherapy followed by EB-DUALNK infusion and safety/response follow-up.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EB-DUALNK following lymphodepleting chemotherapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EB-DUALNK | Biological | (dual-target CAR-NK cells; selected antigen pair from GD2, MUC1, PSMA, mesothelin) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) to determine maximum tolerated dose (MTD) | 28 days | |
| Incidence, severity, and relatedness of adverse events (AEs) | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) per RECIST v1.1. | 12 months | |
| Overall survival (OS) | 12 months |
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Inclusion Criteria:
Exclusion Criteria:
females
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| shan S Lu, Phd | Contact | +86 13076790030 | Seni-Lu@beijing-biotech.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Shenzhen Hospital | Recruiting | Shenzhen | Guangdong | 518036 | China |
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| ID | Term |
|---|---|
| D000077216 | Carcinoma, Ovarian Epithelial |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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Part A: Dose escalation (3+3 design) of EB-DUALNK after lymphodepletion to determine DLTs and RP2D. Part B: Dose expansion at RP2D to further characterize safety and estimate preliminary efficacy.
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Open-label: participants and investigators know the assigned intervention.
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| Cyclophosphamide | Drug | lymphodepletion |
|
| Fludarabine | Drug | lymphodepletion |
|
| D004701 |
| Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |