A Phase 1/2, Open-Label, Dose-Escalation and Expansion Study of Dual-Target CAR-NK Cells (EB-DUALNK) Following Lymphodepleting Chemotherapy in Adults With Recurrent or Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label: participants and investigators know the assigned intervention.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
EB-DUALNK following lymphodepleting chemotherapy
干预措施: EB-DUALNK (Biological)
EB-DUALNK following lymphodepleting chemotherapy
干预措施: Cyclophosphamide (Drug)
EB-DUALNK following lymphodepleting chemotherapy
干预措施: Fludarabine (Drug)