Dual-Target CSPG4/GD2 CAR-NK Cells for Advanced Melanoma (DUET-MEL)

May 31, 2026 updated by: Beijing Biotech

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Dose-escalation safety lead-in
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.
Drug: Cyclophosphamide
Cyclophosphamide
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
Other Names:
  • Fludara
Experimental: Arm B: Cutaneous expansion
Participants with target-positive unresectable/metastatic cutaneous melanoma receive the RP2D after the same lymphodepleting regimen.
Drug: Cyclophosphamide
Cyclophosphamide
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
Other Names:
  • Fludara
Experimental: Arm C:Uveal expansion
Participants with target-positive metastatic uveal melanoma receive the RP2D after the same lymphodepleting regimen.
Drug: Cyclophosphamide
Cyclophosphamide
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
Other Names:
  • Fludara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0
Time Frame: 28 Days
28 Days
Recommended Phase 2 Dose (RP2D)
Time Frame: 42 Days
42 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 24 Months
24 Months
Treatment-emergent adverse events ( TEDE )
Time Frame: 12 Month
Treatment-emergent adverse events including CRS, ICANS, prolonged cytopenias, neuropathic pain, ocular toxicity, and GVHD
12 Month
Objective response rate (ORR) by RECIST v1.1
Time Frame: 12 Month
12 Month
Disease control rate (DCR) by RECIST v1.1
Time Frame: 12 Month
12 Month
Duration of response
Time Frame: 24 Month
24 Month
Progression-free survival (PFS)
Time Frame: 24 Month
24 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

June 14, 2027

Study Completion (Estimated)

June 17, 2028

Study Registration Dates

First Submitted

May 31, 2026

First Submitted That Met QC Criteria

May 31, 2026

First Posted (Actual)

June 4, 2026

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

May 31, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-MEL-DTKN-007

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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