Actively Recruiting
EV-PRIME: Phase Ib/II Study of Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy as a Bladder-Sparing Trimodality Therapy in Muscle Invasive Bladder Cancer
Led by University of California, San Francisco · Updated on 2026-02-18
47
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
U
University of California, San Francisco
Lead Sponsor
A
Astellas Pharma Inc
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, best dosing, and effectiveness of combining enfortumab vedotin with pembrolizumab and radiation therapy to treat patients with muscle invasive bladder cancer. This phase Ib/II trial focuses on patients who are not candidates for standard chemotherapy and surgery or prefer bladder-sparing options. Enfortumab vedotin is a targeted antibody-drug conjugate, and pembrolizumab is an immunotherapy drug that may help the immune system attack cancer cells. The radiation therapy used is intensity-modulated to minimize damage to healthy tissue while targeting the tumor. Participants receive different dose levels of enfortumab vedotin intravenously on days 1 and 8 of 21-day cycles, combined with pembrolizumab given intravenously on day 1 of each cycle. Radiation therapy is delivered once daily for 32 days during the first treatment cycle. The study includes up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab, alongside standard procedures like transurethral resection of bladder tumor (TURBT), cystoscopy, and imaging. Dose escalation occurs in phase Ib, followed by a dose expansion phase II at the recommended phase II dose. Throughout the study, participants undergo regular assessments including cystoscopy, TURBT, cytology, and imaging to evaluate tumor response and safety. Follow-up visits happen 90 days after treatment completion and then every 12 weeks for up to 5 years. Researchers measure clinical complete response rates, recurrence-free survival, cystectomy-free survival, overall survival, and tumor downstaging. Exploratory analyses include changes in tumor gene expression, immune cell populations, and markers related to treatment effects.
CONDITIONS
Brief Title
Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a) with urothelial histology or mixed histologies excluding small cell/neuroendocrine
- Ineligible for or choosing not to undergo radical cystectomy (bladder removal surgery)
- Eligible for bladder irradiation and agree to receive it
- Underwent transurethral resection of bladder tumor (TURBT) within 8 weeks before treatment start with viable tumor content
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate blood counts: neutrophils ≥ 1,500/mcL, platelets ≥ 100,000/mcL, hemoglobin ≥ 9.0 g/dL without recent transfusion
- Liver function within specified limits (bilirubin, AST, ALT)
- Kidney function with creatinine clearance ≥ 30 mL/min/1.73 m²
- Blood clotting times within acceptable ranges
- Ability to understand and sign informed consent
- HIV-positive patients on effective anti-retroviral therapy with undetectable viral load
- Hepatitis B or C patients meeting specific treatment and viral load criteria
- Use of adequate contraception during study participation as required
You will not qualify if you...
- Presence of distant metastases (M1) or extensive lymph node involvement (≥ N2)
- Small cell or neuroendocrine tumor histology
- Absence of urothelial histology (pure variant histology)
- Untreated upper tract urothelial cancer
- Severe hydronephrosis preventing therapy
- Extensive carcinoma in situ (CIS) excluding moderate CIS suitable for radiation
- Baseline neuropathy grade 2 or higher
- Uncontrolled diabetes mellitus with specific criteria
- Prior systemic immunotherapy or chemotherapy for urothelial cancer within 12 months
- Recent anti-cancer therapy or radiotherapy within specified timeframes
- Recent live vaccine administration
- Major surgery within 2 weeks before first study dose
- Immunodeficiency or high-dose immunosuppressive therapy
- History of Kaposi's sarcoma or Multicentric Castleman's Disease in HIV-positive patients
- Active brain metastases or carcinomatous meningitis
- Other significant life-limiting malignancy requiring treatment within 2 years
- Allergies to study drugs or their components
- Prior allogeneic stem cell or organ transplant
- History or current pneumonitis or interstitial lung disease requiring steroids
- Active infection needing systemic treatment
- Conditions or therapies interfering with study participation
- Active hepatitis B or C infection with detectable viral load
- Psychiatric or substance abuse disorders interfering with trial cooperation
- Pregnancy or breastfeeding
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 14 months depending on pembrolizumab cycles
Participants receive enfortumab vedotin intravenously on days 1 and 8 of each 21-day cycle for up to 5 cycles, and pembrolizumab intravenously on day 1 of each cycle for up to 17 cycles. Concurrently, participants undergo standard of care intensity modulated radiation therapy once daily for 32 days over 6.5 to 8 weeks. Participants also undergo transurethral resection of bladder tumor (TURBT), cystoscopy, and imaging throughout the treatment period.
Multiple visits including enfortumab vedotin dosing on days 1 and 8 of each 21-day cycle, pembrolizumab dosing on day 1 of each cycle, daily radiation therapy visits for 6.5 to 8 weeks, and regular cystoscopy and imaging assessments
Duration - Up to 5 years
After completion of study treatment, participants are followed up to monitor safety and response, including cystoscopy, transurethral resection of bladder tumor (TURBT), cytology, and imaging assessments.
Follow-up visits at 90 days post-treatment, then every 12 weeks for up to 5 years
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
Research Team
U
UCSF Genitourinary Medical Oncology Recruitment
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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