Unresectable MelanomaPhase 1/2DUET-MELNCT07627698
Dual-Target CSPG4/GD2 CAR-NK Cells for Advanced Melanoma
A Phase 1/2 study testing EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Fludarabine and Cyclophosphamide in people with Unresectable Melanoma and Metastatic Cutaneous Melanoma, run by Beijing Biotech at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unresectable Melanoma, Metastatic Cutaneous Melanoma, Metastatic Uveal Melanoma
- What is being tested?
- EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2026to 17 Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Zhen J Peng, Phd, +86 13076790039, Zhen-Peng@beijing-biotech.com
About this study
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
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
Read the 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.
- Being tested
- EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Fludarabine, Cyclophosphamide
- Keywords
- CAR-NK, allogeneic NK cells, CSPG4, GD2, advanced melanoma, uveal melanoma, cell therapy, biomarker-guided, solid tumor
- Medical subject headings
- Melanoma, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cellsBiological
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.
FludarabineDrug
Also called Fludara
Fludara
CyclophosphamideDrug
Cyclophosphamide
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0
Measured: 28 Days
Recommended Phase 2 Dose (RP2D)
Measured: 42 Days
Secondary outcomes (6)
Treatment-emergent adverse events ( TEDE )
Treatment-emergent adverse events including CRS, ICANS, prolonged cytopenias, neuropathic pain, ocular toxicity, and GVHD
Measured: 12 Month
Objective response rate (ORR) by RECIST v1.1
Measured: 12 Month
Disease control rate (DCR) by RECIST v1.1
Measured: 12 Month
Duration of response
Measured: 24 Month
Progression-free survival (PFS)
Measured: 24 Month
Overall survival
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2026
- Study start2 Mar 2026
- Primary completion14 Jun 2027 (estimated)
- Study completion17 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable MelanomaStudies of the same condition, open and under way.
- More trials run by Beijing BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07627698
- Sponsor's protocol ID
- EB-MEL-DTKN-007
- Acronym
- DUET-MEL
- Status last verified
- May 2026
- First submitted
- 31 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07627698
- Acronym / sponsor ID
- DUET-MEL / EB-MEL-DTKN-007
- Keywords
- CAR-NK, allogeneic NK cells, CSPG4, GD2, advanced melanoma, uveal melanoma, cell therapy, biomarker-guided
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2026 (actual)
- Primary completion
- 14 Jun 2027 (estimated)
- Study completion
- 17 Jun 2028 (estimated)
- First posted
- 4 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm A: Dose-escalation safety lead-in | Experimental | Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Drug: Fludarabine, Drug: CyclophosphamideTarget-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. |
| Arm B: Cutaneous expansion | Experimental | Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Drug: Fludarabine, Drug: CyclophosphamideParticipants with target-positive unresectable/metastatic cutaneous melanoma receive the RP2D after the same lymphodepleting regimen. |
| Arm C:Uveal expansion | Experimental | Biological: EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Drug: Fludarabine, Drug: CyclophosphamideParticipants with target-positive metastatic uveal melanoma receive the RP2D after the same lymphodepleting regimen. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cellsGenetically 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. | Biological | Arm A: Dose-escalation safety lead-in, Arm B: Cutaneous expansion, Arm C:Uveal expansion |
| FludarabineAlso: FludaraFludara | Drug | Arm A: Dose-escalation safety lead-in, Arm B: Cutaneous expansion, Arm C:Uveal expansion |
| CyclophosphamideCyclophosphamide | Drug | Arm A: Dose-escalation safety lead-in, Arm B: Cutaneous expansion, Arm C:Uveal expansion |
Primary outcome
Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0
Time frame: 28 Days
Recommended Phase 2 Dose (RP2D)
Time frame: 42 Days
6 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EB-DTKN-401 allogeneic dual-target CSPG4/GD2 CAR-NK cells, Fludarabine and Cyclophosphamide in people with Unresectable Melanoma and Metastatic Cutaneous Melanoma, run by Beijing Biotech at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Seni S Lu, Phd (+86 13076790030, Seni-Lu@beijing-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) using CTCAE v5.0 (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.