Bladder CancerPhase 1DUET-UC-NKNCT07492628
Dual-Target Nectin-4/HER2 CAR-NK Cells in Advanced Urothelial Carcinoma
A Phase 1 study testing EB-DT-NK-UC101, Cyclophosphamide and Fludarabine in people with Bladder Cancer and Urothelial Carcinoma, run by Beijing Biotech at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma
- What is being tested?
- EB-DT-NK-UC101, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2026to 17 May 2028
- Phase
- Phase 1
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 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.
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- 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.
Who cannot join
- 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).
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- 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.
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: 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
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 validation; HER2/ERBB2 was chosen as the secondary co-target to broaden tumor coverage and reduce antigen-escape risk. EpCAM is not selected as a therapeutic co-target in this example because of broader normal epithelial expression and weaker tumor specificity in urothelial carcinoma.
Read the 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 uses mandatory pre-treatment central biomarker testing and favors fresh biopsy after the most recent systemic therapy, especially after prior enfortumab vedotin or HER2-directed treatment.
The investigational product in this example is an allogeneic cord-blood-derived CAR-NK cell therapy engineered to co-recognize Nectin-4 and HER2/ERBB2 and to include an inducible caspase-9 safety switch. The product is administered intravenously after lymphodepletion with fludarabine and cyclophosphamide. Part A uses a 3+3 dose-escalation design with sentinel dosing at each new level to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Part B expands the RP2D to better characterize safety and generate preliminary efficacy data.
To better address the original target shortlist, the protocol also incorporates exploratory translational analyses of EpCAM expression, circulating tumor DNA, tumor antigen co-expression, NK-cell persistence, and mechanisms of resistance. This allows future protocol versions to revisit EpCAM only if patient-specific biomarker data show a favorable therapeutic window.
Tumor assessments are performed by RECIST v1.1 for measurable metastatic disease.
Patients are monitored closely for dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), graft-versus-host disease (GvHD), infusion reactions, and organ-specific on-target/off-tumor toxicities. Because HER2 is used as a secondary antigen, this example explicitly incorporates enhanced cardiopulmonary monitoring and conservative dose-escalation rules.
- Conditions
- Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Upper Tract Urothelial Carcinoma
- Being tested
- EB-DT-NK-UC101, Cyclophosphamide, Fludarabine
- Keywords
- CAR-NK, allogeneic NK cells, Nectin-4, HER2, ERBB2, urothelial carcinoma, bladder cancer, dual-target, lymphodepletion, solid tumor immunotherapy, EpCAM, RP2D
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-DT-NK-UC101Biological
Allogeneic cord-blood-derived dual-target Nectin-4/HER2 CAR-NK cells with inducible caspase-9 safety switch.
CyclophosphamideDrug
Lymphodepleting chemotherapy given before the first CAR-NK infusion.
FludarabineDrug
Also called lymphodepletion
Lymphodepleting chemotherapy given before the first CAR-NK infusion
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | 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 Receives: Biological: EB-DT-NK-UC101; Drug: Cyclophosphamide; Drug: Fludarabine |
| Dose Expansion | Experimental | 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. Receives: Biological: EB-DT-NK-UC101; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Measured: 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
Measured: 12 months
Secondary outcomes (5)
Objective response rate (ORR) by RECIST v1.1
Measured: 12 months
Disease control rate
Measured: 12 months
Duration of response
Measured: 24 months
Progression-free survival
Measured: 24 months
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 posted25 Mar 2026
- Study start2 Mar 2026
- Primary completion14 Jun 2027 (estimated)
- Study completion17 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Part A: 3+3 dose-escalation with sentinel dosing of allogeneic dual-target Nectin-4/HER2 CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion to determine MTD/RP2D. Part B: dose-expansion at RP2D to further define safety, feasibility, and preliminary anti-tumor activity in biomarker-positive urothelial carcinoma
- Masking
- None (open label)
- Enrolment
- 42 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
- NCT07492628
- Sponsor's protocol ID
- EB-DT-NK-UC-105
- Acronym
- DUET-UC-NK
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2026
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No