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Clinical Trial NCT07492628 (DUET-UC-NK) for Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Upper Tract Urothelial Carcinoma is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Dual-Target Nectin-4/HER2 CAR-NK Cells in Advanced Urothelial Carcinoma (DUET-UC-NK) Phase 1 42 First-in-Human

Recruiting
Clinical Trial NCT07492628 (DUET-UC-NK) is designed to study Treatment for Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Upper Tract Urothelial Carcinoma. It is a Phase 1 interventional study that is recruiting, having started on 2 March 2026, with plans to enroll 42 participants. Led by Beijing Biotech, it is expected to complete by 17 May 2028. The latest data from ClinicalTrials.gov was last updated on 25 March 2026.
Brief Summary
This hypothetical first-in-human study is designed to evaluate the safety, feasibility, and preliminary anti-tumor activity of an allogeneic dual-target Nectin-4/HER2 CAR-NK cell product in adults with relapsed/refractory locally advanced or metastatic urothelial carcinoma. Based on public urothelial-cancer evidence, Nectin-4 was selected as the lead antigen because it has the strongest disease-specific clinical vali...Show More
Detailed Description
Advanced urothelial carcinoma remains a high-unmet-need disease after platinum-based chemotherapy, PD-1/PD-L1 inhibition, and-where available-Nectin-4- or HER2-directed therapies. Public trial activity in urothelial cancer strongly supports Nectin-4 as the best validated anchor antigen, while HER2 identifies a clinically relevant and actionable subset. Because both antigens can be heterogeneous, this example protocol...Show More
Official Title

A Phase 1, Open-Label, Multicenter, Non-Randomized, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target Nectin-4/HER2 CAR-NK Cells Following Fludarabine/Cyclophosphamide Lymphodepletion in Adults With Relapsed/Refractory, Locally Advanced or Metastatic Urothelial Carcinoma

Conditions
Bladder CancerUrothelial CarcinomaMetastatic Urothelial CarcinomaLocally Advanced Urothelial CarcinomaUpper Tract Urothelial Carcinoma
Other Study IDs
  • DUET-UC-NK
  • EB-DT-NK-UC-105
NCT ID Number
NCT07492628
Start Date (Actual)
2026-03-02
Last Update Posted
2026-03-25
Completion Date (Estimated)
2028-05-17
Enrollment (Estimated)
42
Study Type
Interventional
PHASE
Phase 1
Status
Recruiting
Keywords
CAR-NK
allogeneic NK cells
Nectin-4
HER2
ERBB2
urothelial carcinoma
bladder cancer
dual-target
lymphodepletion
solid tumor immunotherapy
EpCAM
RP2D
Primary Purpose
Treatment
Design Allocation
Non-Randomized
Interventional Model
Sequential
Masking
None (Open Label)
Arms / Interventions
Participant Group/ArmIntervention/Treatment
ExperimentalDose Escalation
Participants receive lymphodepletion with cyclophosphamide and fludarabine followed by EB-DT-NK-UC101 IV infusions on Day 1 and Day 8 of a 21-day cycle. Planned dose levels: 1 × 10\^7, 3 × 10\^7, and 1 × 10\^8 CAR-NK cells/kg
EB-DT-NK-UC101
Allogeneic cord-blood-derived dual-target Nectin-4/HER2 CAR-NK cells with inducible caspase-9 safety switch.
Cyclophosphamide
Lymphodepleting chemotherapy given before the first CAR-NK infusion.
Fludarabine
Lymphodepleting chemotherapy given before the first CAR-NK infusion
ExperimentalDose Expansion
Participants receive the RP2D identified in Arm A using the same lymphodepletion backbone and infusion schedule. Expansion enriches for Nectin-4-positive disease and captures HER2 co-expression prospectively.
EB-DT-NK-UC101
Allogeneic cord-blood-derived dual-target Nectin-4/HER2 CAR-NK cells with inducible caspase-9 safety switch.
Cyclophosphamide
Lymphodepleting chemotherapy given before the first CAR-NK infusion.
Fludarabine
Lymphodepleting chemotherapy given before the first CAR-NK infusion
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
Incidence of dose-limiting toxicities (DLTs)
28 Days
Incidence and severity of treatment-emergent adverse
Incidence and severity of treatment-emergent adverse events graded by CTCAE v5.0,including CRS, ICANS, infusion reactions, GvHD, and organ-specific toxicities
12 months
Secondary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
Objective response rate (ORR) by RECIST v1.1
12 months
Disease control rate
12 months
Duration of response
24 months
Progression-free survival
24 months
Overall survival
24 months
Participation Assistant
Eligibility Criteria

Eligible Ages
Adult, Older Adult
Minimum Age
18 Years
Eligible Sexes
All
  • Age 18-75 years at consent.
  • Histologically confirmed urothelial carcinoma of the bladder, ureter, renal pelvis, or urethra that is unresectable locally advanced or metastatic.
  • Disease progression after, intolerance to, or ineligibility for standard therapy, including platinum-based chemotherapy and PD-1/PD-L1 blockade when appropriate for the patient and region. Prior enfortumab vedotin and prior HER2-directed therapy are allowed, but a fresh biopsy is strongly preferred after the latest systemic regimen.
  • At least one measurable lesion per RECIST v1.1.
  • Tumor tissue available for central review demonstrating Nectin-4 positivity (for example, IHC ≥1+ in ≥10% tumor cells) and HER2 status assessed by IHC/ISH. At least one of the selected therapeutic targets must be present; dose expansion preferentially enrolls Nectin-4-positive disease.
  • ECOG performance status 0-1.
  • Adequate bone marrow, hepatic, renal, and coagulation function.
  • Life expectancy of at least 12 weeks.
  • Negative pregnancy test for women of childbearing potential and agreement to use highly effective contraception during study treatment and follow-up as defined in the protocol.
  • Ability to understand and sign informed consent.

  • Active or untreated central nervous system metastases or leptomeningeal disease. Previously treated CNS disease is allowed if clinically stable and off escalating corticosteroids.
  • Prior allogeneic hematopoietic stem cell transplant, prior solid-organ transplant, or active graft-versus-host disease.
  • Clinically significant autoimmune disease requiring systemic immunosuppression within the defined washout window.
  • Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, sepsis, or active tuberculosis.
  • Clinically significant cardiac disease, active myocarditis, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful decline in left ventricular ejection fraction that would increase risk from HER2-directed cell therapy.
  • Clinically significant pulmonary disease (for example, uncontrolled interstitial lung disease or oxygen-dependent respiratory compromise).
  • Use of systemic corticosteroids or other immunosuppressive medications above protocol-allowed limits within the washout window.
  • History of severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients.
  • Pregnancy or breastfeeding.
  • Another active malignancy requiring systemic therapy or likely to interfere with protocol assessments, except for protocol-allowed low-risk cancers.
Beijing Biotech logoBeijing Biotech
Study Central Contact
Contact: Seni S Lu, Phd, +86 13076790030, [email protected]
1 Study Locations in 1 Countries

Guangdong

Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China
Zhen J Peng, Phd, Contact, +86 13076790039, [email protected]
Recruiting