An Open-Label, Multicenter Phase 1/2 Study of Allogeneic Dual-Target CSPG4/GD2 CAR-NK Cells (EB-DTKN-401) in Adults With Unresectable or Metastatic Cutaneous Melanoma or Metastatic Uveal Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 1
研究概览
简要总结
This is a first-in-human, open-label, multicenter phase 1/2 study evaluating the safety, feasibility, recommended phase 2 dose (RP2D), and preliminary antitumor activity of allogeneic dual-target CSPG4/GD2 CAR-NK cells (EBDTKN-401) after lymphodepleting chemotherapy in adults with unresectable or metastatic cutaneous melanoma or metastatic uveal melanoma whose disease has progressed after standard therapy
详细描述
The target-selection review favored CSPG4/GD2 because it gives the strongest melanoma-centered rationale across both cutaneous and uveal disease. EBDTKN-401 is an allogeneic donor-derived NK-cell product engineered with an OR-gate/tandem CAR recognizing CSPG4 or GD2 and an inducible caspase-9 safety switch. Part A uses 3+3 dose escalation to identify the RP2D. Part B evaluates the RP2D in expansion cohorts for cutaneous melanoma and uveal melanoma. Key secondary objectives are objective response, disease control, durability, progression-free survival, overall survival, CAR-NK persistence, and baseline biomarker-response relationships.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label conduct is appropriate because cell-product identity, dose level, and near-real-time toxicity management must remain visible to investigators and treating teams in a first-in-human adoptive cell-therapy study.
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 18-75 years at consent.
- •Histologically confirmed unresectable/metastatic cutaneous melanoma or metastatic uveal melanoma.
- •Disease progression after standard therapy, intolerance to standard therapy, or no remaining standard option expected to provide meaningful benefit. For cutaneous melanoma: prior anti-PD-1/L1 (with or without antiCTLA-4) unless contraindicated; if BRAF V600-mutant, prior BRAF/MEK inhibitor therapy or documented unsuitability. For uveal melanoma: prior tebentafusp if HLA-A*02:01-positive and eligible, or documented unsuitability/unavailability plus at least one prior systemic therapy.
- •Tumor demonstrates CSPG4 and/or GD2 expression in archival or fresh tissue by central testing (suggested positivity threshold: at least 25% viable tumor cells by IHC or equivalent validated assay).
- •At least 1 measurable lesion by RECIST v1.
- •ECOG performance status 0-
- •Adequate bone marrow, renal, hepatic, cardiac, and pulmonary function per protocol.
- •Life expectancy of at least 12 weeks.
- •Treated, stable brain metastases are allowed if neurologically stable for at least 4 weeks and not requiring escalating corticosteroids.
- •Willingness to use effective contraception and comply with protocol-required visits, blood sampling, and requested biopsies.
排除标准
- •Active symptomatic CNS metastases, leptomeningeal disease, or uncontrolled seizure disorder.
- •Prior allogeneic stem cell transplant or solid organ transplant; prior gene-modified cellular therapy within 12 weeks; or anti-cancer therapy too close to lymphodepletion per protocol washout rules.
- •Requirement for systemic immunosuppression greater than 10 mg prednisone equivalent/day or uncontrolled autoimmune/inflammatory disease requiring systemic treatment.
- •Active uncontrolled infection, including uncontrolled HIV, HBV, or HCV, or fever/sepsis at the time lymphodepletion would begin.
- •Clinically significant cardiovascular disease, uncontrolled arrhythmia, recent myocardial infarction, or uncontrolled thromboembolic disease.
- •Grade 2 or higher unresolved toxicities from prior therapy, except stable endocrinopathy, alopecia, or vitiligo.
- •Pregnancy or breastfeeding.
- •Any condition that, in the investigator's judgment, would make lymphodepletion or CAR-NK infusion unsafe.