A Phase 1/2, Open-Label, Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of EB-NK-301 (Allogeneic TROP2-Targeted CAR NK Cells) Following Lymphodepleting Chemotherapy in Adults With Advanced or Metastatic TROP2-Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) (CTCAE v5.0)
研究概览
简要总结
study evaluates EB-NK-301, an investigational off-the-shelf allogeneic CAR-NK cell product targeting TROP2, in adults with advanced or metastatic solid tumors that express TROP2 and have progressed after standard therapy.
The primary goals are to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine a recommended Phase 2 dose (RP2D). Secondary goals include preliminary anti-tumor activity, persistence of infused CAR-NK cells, and exploratory immune biomarkers.
详细描述
Study Overview: The study includes two parts. Part A (dose escalation) uses a standard dose-escalation design to evaluate multiple dose levels of EB-NK-301 after lymphodepleting chemotherapy. Part B (dose expansion) enrolls additional participants at the selected RP2D to further characterize safety and to estimate preliminary efficacy within selected tumor-type cohorts.
Treatment Plan: Participants receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by intravenous EB-NK-301 infusions. Participants are monitored closely for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, and other adverse events.
Assessments: Tumor imaging is performed every 8 weeks during the first 12 months, then every 12 weeks as clinically indicated. Blood samples are collected to assess CAR-NK cell persistence, cytokines, and other immune biomarkers.
Follow-up: Participants are followed for safety and survival for up to 24 months after first infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label study. Participants, investigators, and study staff are aware of the assigned intervention.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years at the time of informed consent.
- •Histologically or cytologically confirmed advanced or metastatic solid tumor with documented TROP2 expression (per local testing or central confirmation).
- •Disease progression on, intolerance to, or ineligibility for available standard therapy.
- •At least one measurable lesion per RECIST 1.
- •ECOG performance status 0 to
- •Adequate organ function (hematologic, renal, hepatic) within protocol-defined limits.
- •Life expectancy ≥ 12 weeks.
- •Willingness to use effective contraception during study participation and for a protocol-defined period after last infusion (if of childbearing potential).
- •Ability to understand and willingness to sign written informed consent.
排除标准
- •Active central nervous system (CNS) metastases or leptomeningeal disease (unless treated and clinically stable for ≥ 4 weeks).
- •Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
- •Uncontrolled active infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.
- •Active autoimmune disease requiring systemic immunosuppression.
- •Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke within 6 months, uncontrolled arrhythmia).
- •Receipt of another investigational agent within 2 weeks (or 5 half-lives, whichever is longer) prior to lymphodepleting chemotherapy.
- •Prior gene-modified cellular therapy within 3 months prior to enrollment.
- •Systemic corticosteroid therapy > 10 mg/day prednisone equivalent within 7 days prior to lymphodepletion (excluding physiologic replacement).
- •Pregnant or breastfeeding.
研究组 & 干预措施
Dose Escalation
Sequential dose escalation of EB-NK-301 following lymphodepleting chemotherapy to evaluate safety, DLTs, and identify RP2D.
干预措施: EB-NK-301 (Biological)
Dose Expansion
Expansion cohorts at the RP2D in selected TROP2-expressing tumor types to further assess safety and preliminary efficacy.
干预措施: EB-NK-301 (Biological)
Dose Escalation
Sequential dose escalation of EB-NK-301 following lymphodepleting chemotherapy to evaluate safety, DLTs, and identify RP2D.
干预措施: Fludarabine (Drug)
Dose Expansion
Expansion cohorts at the RP2D in selected TROP2-expressing tumor types to further assess safety and preliminary efficacy.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) (CTCAE v5.0)
时间窗: 28 days
Incidence and severity of treatment-emergent adverse events (AEs)
时间窗: 12 months
Recommended Phase 2 dose (RP2D) of EB-NK-301
时间窗: 6 months
次要结局
- Objective response rate (ORR) per RECIST 1.1(12 months)
- Duration of response (DoR)(24 months)
- Overall survival (OS)(24 months)