Dual-Target CSPG4/GD2 CAR-NK Cells for Advanced Melanoma

NCT07627698 | Recruiting Phase 1 DMC

• 1 other identifier: EB-MEL-DTKN-007
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Unresectable Melanoma; Metastatic Cutaneous Melanoma; Metastatic Uveal Melanoma

Keywords

CAR-NK; allogeneic NK cells; CSPG4; GD2; advanced melanoma; uveal melanoma; cell therapy; biomarker-guided; solid tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0

  28 Days

• Recommended Phase 2 Dose (RP2D)

  42 Days

Secondary Outcomes (6)

• Treatment-emergent adverse events ( TEDE )

  12 Month

• Objective response rate (ORR) by RECIST v1.1

  12 Month

• Disease control rate (DCR) by RECIST v1.1

  12 Month

• Duration of response

  24 Month

• Progression-free survival (PFS)

  24 Month

Study Arms (3)

Arm A: Dose-escalation safety lead-in

EXPERIMENTAL

Target-positive adults with unresectable/metastatic cutaneous melanoma or metastatic uveal melanoma receive lymphodepletion followed by EB-DTKN-401 at one of three planned dose levels; up to three infusions over 15 days.

Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide

Arm B: Cutaneous expansion

EXPERIMENTAL

Participants with target-positive unresectable/metastatic cutaneous melanoma receive the RP2D after the same lymphodepleting regimen.

Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide

Arm C:Uveal expansion

EXPERIMENTAL

Participants with target-positive metastatic uveal melanoma receive the RP2D after the same lymphodepleting regimen.

Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells BIOLOGICAL

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.

Arm A: Dose-escalation safety lead-in; Arm B: Cutaneous expansion; Arm C:Uveal expansion

Fludarabine DRUG

Fludara

Also known as: Fludara

Arm A: Dose-escalation safety lead-in; Arm B: Cutaneous expansion; Arm C:Uveal expansion

Cyclophosphamide DRUG

Cyclophosphamide

Arm A: Dose-escalation safety lead-in; Arm B: Cutaneous expansion; Arm C:Uveal expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A uses a 3+3 dose-escalation design across three planned dose levels (1×10\^7, 3×10\^7, and 1×10\^8 CAR-NK cells/kg). After RP2D selection, Part B opens parallel subtype-specific expansion cohorts for cutaneous melanoma and uveal melanoma at the RP2D. Participants are not randomized.

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 4, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): June 17, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-05

Locations

CN (1)