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
- 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 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.
- 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
- 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
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07492628
- Acronym / sponsor ID
- DUET-UC-NK / EB-DT-NK-UC-105
- Conditions
- Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Upper Tract Urothelial Carcinoma
- Keywords
- CAR-NK, allogeneic NK cells, Nectin-4, HER2, ERBB2, urothelial carcinoma, bladder cancer, dual-target
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2026 (actual)
- Primary completion
- 14 Jun 2027 (estimated)
- Study completion
- 17 May 2028 (estimated)
- First posted
- 25 Mar 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 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Biological: EB-DT-NK-UC101, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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 |
| Dose Expansion | Experimental | Biological: EB-DT-NK-UC101, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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. |
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 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.
Key exclusion criteria (10 listed)
- 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.
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-DT-NK-UC101Allogeneic cord-blood-derived dual-target Nectin-4/HER2 CAR-NK cells with inducible caspase-9 safety switch. | Biological | Dose Escalation, Dose Expansion |
| CyclophosphamideLymphodepleting chemotherapy given before the first CAR-NK infusion. | Drug | Dose Escalation, Dose Expansion |
| FludarabineAlso: lymphodepletionLymphodepleting chemotherapy given before the first CAR-NK infusion | Drug | Dose Escalation, Dose Expansion |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Incidence and severity of treatment-emergent adverse
Time frame: 12 months
Incidence and severity of treatment-emergent adverse events graded by CTCAE v5.0,including CRS, ICANS, infusion reactions, GvHD, and organ-specific toxicities
5 secondary outcomes
Objective response rate (ORR) by RECIST v1.1
Time frame: 12 months
Disease control rate
Time frame: 12 months
Duration of response
Time frame: 24 months
Progression-free survival
Time frame: 24 months
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 25 Mar 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 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.
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 10 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 25 Mar 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 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.
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) (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 25 Mar 2026.