Dual-Target Nectin-4/HER2 CAR-NK Cells in Advanced Urothelial Carcinoma

Recruiting now · Phase 1

Conditions studied: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Upper Tract Urothelial Carcinoma

In brief

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.

Key facts

Study ID

NCT07492628

Run by

Beijing Biotech

People needed

42

Starts

2026-03-02

Expected to finish

2028-05-17

Last updated by the study team

2026-03-25

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (enrolling)

Full record on ClinicalTrials.gov

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