Dual-Target CSPG4/GD2 CAR-NK Cells for Advanced Melanoma
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Fludarabine, Cyclophosphamide.
- Who it may be relevant to
- Registry conditions: Unresectable Melanoma, Metastatic Cutaneous Melanoma, Metastatic Uveal Melanoma. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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
Detailed description
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.
Interventions
- Biological EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells
Genetically engineered natural killer (NK) cells expressing dual chimeric antigen receptors targeting CSPG4 and GD2 are expanded ex vivo and infused (IV) into patients. These cells recognize tumor antigens and induce targeted cytotoxicity, aiming to improve tumor killing and reduce antigen escape in CSPG4/GD2-positive cancers. - Drug Fludarabine
Fludara - Drug Cyclophosphamide
Cyclophosphamide
Primary outcome measures
- Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0 [Time frame: 28 Days]
- Recommended Phase 2 Dose (RP2D) [Time frame: 42 Days]
Secondary outcome measures (6)
- Treatment-emergent adverse events ( TEDE ) [Time frame: 12 Month]
- Objective response rate (ORR) by RECIST v1.1 [Time frame: 12 Month]
- Disease control rate (DCR) by RECIST v1.1 [Time frame: 12 Month]
- Duration of response [Time frame: 24 Month]
- Progression-free survival (PFS) [Time frame: 24 Month]
- Overall survival [Time frame: 24 Months]
Eligibility criteria
Inclusion criteria
- 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 v1.1.
- ECOG performance status 0-1.
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Peking University Shenzhen Hospital — Shenzhen
Identifiers
NCT: NCT07627698 · EB-MEL-DTKN-007