Dual-target Nectin-4 and HER2 CAR-NK therapy for advanced urothelial carcinoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This first-in-human Phase 1 protocol uses allogeneic cord-blood-derived CAR-NK cells engineered to co-recognize Nectin‑4 and HER2 and to include an inducible caspase‑9 safety switch. Patients receive lymphodepletion with fludarabine and cyclophosphamide followed by intravenous infusion of the CAR‑NK product; Part A follows a 3+3 dose-escalation with sentinel dosing and Part B expands at the recommended dose. Mandatory central biomarker testing (preferably on a fresh biopsy) determines Nectin‑4/HER2 status and preferentially enrolls Nectin‑4-positive disease for dose expansion. The protocol includes exploratory translational studies such as EpCAM expression, circulating tumor DNA, tumor antigen co-expression, NK-cell persistence, and resistance mechanisms.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: Seni S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.