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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
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.
Fludara
Cyclophosphamide
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs) using CTCAE v5.0
Time frame: 28 Days
Recommended Phase 2 Dose (RP2D)
Time frame: 42 Days
Treatment-emergent adverse events ( TEDE )
Treatment-emergent adverse events including CRS, ICANS, prolonged cytopenias, neuropathic pain, ocular toxicity, and GVHD
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.