A Phase 1/2, Open-Label, Biomarker-Driven Study of Allogeneic Donor-Derived CAR-NK Cells With Antigen Selection by Tissue Biopsy and/or Liquid Biopsy Profiling in Participants With Relapsed/Refractory Advanced Solid Tumors (Single-Target vs Dual-Target Strategy)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0
研究概览
简要总结
This Phase 1/2 study evaluates the safety, feasibility, and preliminary anti-tumor activity of allogeneic donor-derived CAR-NK cells in participants with advanced solid tumors. The CAR target antigen is selected for each participant after tumor profiling using a tissue biopsy and/or liquid biopsy. Participants will receive either a single-target or dual-target CAR-NK product based on the antigen profile.
详细描述
This is an open-label, biomarker-driven adoptive cell therapy study.
Screening / Target Selection (Precision Step):
Participants undergo tumor antigen profiling using:
Tissue biopsy (preferred when safely feasible), and/or Liquid biopsy (e.g., circulating tumor DNA plus circulating tumor cells/exosome protein assay, as available in the platform).
Antigen profiling determines eligibility and assigns participants to:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label due to the nature of personalized antigen assignment and cell product differences
入排标准
- 年龄范围
- 8 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years.
- •Histologically or cytologically confirmed advanced/unresectable or metastatic solid tumor that is relapsed/refractory after standard therapy, or no standard therapy available.
- •Targetable antigen positivity from the protocol target menu based on:
- •tissue biopsy and/or liquid biopsy platform (as defined in the lab manual).
- •Arm assignment rules :
- •Arm A: ≥1 antigen meets "positive" threshold
- •Arm B: ≥2 antigens meet "positive" threshold
- •ECOG performance status 0-1 (or 0-2 ).
- •At least one measurable lesion by RECIST 1.
- •Adequate organ function (hematologic, renal, hepatic, cardiac) within protocol-defined limits.
- •Willingness to undergo blood draws and required biopsies (when medically feasible).
- •Negative pregnancy test for participants of childbearing potential; agreement to effective contraception during and after study treatment.
排除标准
- •Prior treatment with gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within a defined washout period .
- •Active, uncontrolled infection requiring IV antibiotics; known uncontrolled HIV; active HBV/HCV with detectable viral load (per local policy).
- •Active CNS metastases requiring escalating steroids or urgent intervention (stable treated CNS disease may be allowed ).
- •Active autoimmune disease requiring systemic immunosuppression, or chronic systemic steroids above protocol threshold.
- •Clinically significant cardiovascular disease (e.g., recent MI, unstable arrhythmia), uncontrolled pulmonary disease, or other serious comorbidity that increases risk.
- •Major surgery or anticancer therapy too close to lymphodepletion (protocol-defined washout).
- •Pregnant or breastfeeding.
研究组 & 干预措施
Single-Target Antigen-Selected CAR-NK
Participants whose profiling identifies one dominant actionable antigen.
干预措施: EB-SELECT Single-Target CAR-NK Cells (Biological)
Dual-Target Antigen-Selected CAR-NK
Participants whose profiling identifies two actionable antigens, or strong evidence of antigen heterogeneity.
干预措施: Dual-Target Antigen-Selected CAR-NK (Biological)
结局指标
主要结局
Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0
时间窗: 28 DAYS
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 28 DAYS
次要结局
- Objective Response Rate (ORR) (RECIST 1.1)(12 months)
- Disease Control Rate (DCR)(12 months)