Actively Recruiting
Dual-Target Nectin-4/HER2 CAR-NK Cell Therapy with Lymphodepletion in Adults with Relapsed or Refractory Locally Advanced or Metastatic Urothelial Carcinoma
Led by Beijing Biotech · Updated on 2026-03-25
42
Participants Needed
1
Research Sites
48 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying an allogeneic dual-target Nectin-4/HER2 CAR-NK cell therapy in adults with relapsed or refractory locally advanced or metastatic urothelial carcinoma. This phase 1, open-label study aims to evaluate the safety, feasibility, and preliminary anti-tumor activity of this investigational treatment following prior standard therapies including platinum-based chemotherapy and PD-1/PD-L1 inhibitors. The therapy targets two antigens to improve tumor coverage and reduce treatment escape, addressing the high unmet needs in advanced urothelial cancer. The investigational product is an allogeneic cord-blood-derived CAR-NK cell therapy engineered to recognize both Nectin-4 and HER2 antigens, with an inducible safety switch. Patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before intravenous infusions of the CAR-NK cells on Day 1 and Day 8 of each 21-day cycle. The study includes a dose-escalation phase to find the maximum tolerated dose or recommended dose followed by a dose-expansion phase to further assess safety and early efficacy. Participants undergo tumor assessments using RECIST v1.1 criteria for measurable disease and are closely monitored for side effects such as cytokine release syndrome, neurotoxicity, graft-versus-host disease, and infusion reactions. Additional evaluations include biomarker analyses and cardiopulmonary monitoring. The primary outcomes focus on dose-limiting toxicities and adverse event severity over 12 months, with secondary outcomes assessing response rates, disease control, and survival over up to 24 months. The study expects participant involvement over this period with regular safety and efficacy assessments.
CONDITIONS
Brief Title
Dual-Target Nectin-4/HER2 CAR-NK Cells in Advanced Urothelial Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 75 years at consent
- Histologically confirmed urothelial carcinoma of bladder, ureter, renal pelvis, or urethra, unresectable locally advanced or metastatic
- Disease progression after, intolerance to, or ineligibility for standard therapy including platinum chemotherapy and PD-1/PD-L1 blockade
- Prior enfortumab vedotin and HER2-directed therapy allowed; fresh biopsy strongly preferred after latest systemic treatment
- At least one measurable lesion per RECIST v1.1
- Tumor tissue available showing Nectin-4 positivity and HER2 status assessed
- At least one therapeutic target present; dose expansion favors Nectin-4-positive disease
- ECOG performance status 0-1
- Adequate bone marrow, liver, kidney, and coagulation function
- Life expectancy of at least 12 weeks
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception
- Ability to understand and sign informed consent
You will not qualify if you...
- Active or untreated central nervous system metastases or leptomeningeal disease
- Prior allogeneic stem cell transplant, prior solid-organ transplant, or active graft-versus-host disease
- Clinically significant autoimmune disease requiring systemic immunosuppression recently
- Uncontrolled infection including hepatitis B, hepatitis C, HIV, sepsis, or active tuberculosis
- Significant cardiac disease or recent heart events increasing risk
- Clinically significant lung disease or oxygen dependence
- Use of systemic corticosteroids or immunosuppressants above allowed limits recently
- History of severe hypersensitivity to study drugs or product components
- Pregnancy or breastfeeding
- Another active malignancy requiring systemic therapy or interfering with assessments, except low-risk cancers allowed
AI-Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Short period immediately before treatment
Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine before CAR-NK cell infusion.
1 visit (in-person)
Duration - Repeated 21-day cycles until disease progression or discontinuation
Participants receive intravenous infusions of allogeneic cord-blood-derived dual-target Nectin-4/HER2 CAR-NK cells on Day 1 and Day 8 of each 21-day cycle.
2 visits per cycle (in-person)
Duration - Up to 24 months
Participants are monitored for safety and treatment effects including adverse events and tumor response.
Regular visits for assessments during follow-up
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
Seni S Lu, Phd
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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