Actively Recruiting
Pembrolizumab Maintenance After Enfortumab Vedotin/Pembrolizumab Induction in Front-Line Metastatic Urothelial Carcinoma
Led by Fox Chase Cancer Center · Updated on 2026-02-19
97
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
Sponsors
F
Fox Chase Cancer Center
Lead Sponsor
U
United States Department of Defense
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying the effectiveness of a combination treatment using enfortumab vedotin (EV) and pembrolizumab (P) followed by pembrolizumab maintenance therapy in patients who have not previously been treated for metastatic urothelial carcinoma (mUC). This Phase II trial is designed to evaluate the response to this treatment regimen over time, aiming to improve outcomes for patients with this advanced cancer type. Approximately 97 patients will participate in this open-label, non-randomized study. During the 18-week induction phase, patients receive EV intravenously at 1.25 mg/kg on Days 1 and 8 of each 21-day cycle, with a starting dose of 1 mg/kg allowed, plus pembrolizumab at 200 mg IV on Day 1 of each cycle. Radiographic scans assess the cancer after 3 and 6 cycles. Patients who respond with complete or partial remission move to a maintenance phase receiving pembrolizumab at 400 mg IV every 6 weeks or 200 mg IV every 3 weeks for up to 2 years. Dose adjustments for EV are permitted, but pembrolizumab doses remain fixed. Treatment continues until the disease progresses, unacceptable side effects occur, or maintenance therapy ends. Participants will have scans and clinical assessments during and after treatment to monitor cancer status, side effects, and quality of life. If treatment is stopped early due to toxicity or near complete response, patients enter long-term follow-up. Those who experience progression may resume original dosing or enter survival follow-up. The primary outcome measured is 18-month progression-free survival, with secondary outcomes including overall survival, response duration, peripheral neuropathy incidence, and quality of life over four years.
CONDITIONS
Brief Title
Pembrolizumab Maintenance After Enfortumab Vedotin (EV)/Pembro Induction in Front-Line Metastatic Urothelial Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have histologically and radiographically confirmed locally advanced, unresectable urothelial carcinoma.
- No prior systemic therapy for metastatic disease.
- Measurable disease with at least one lesion measurable per RECIST v1.1.
- Prior neoadjuvant or adjuvant immune checkpoint inhibitor therapy allowed if completed at least 12 months prior.
- ECOG performance status 0-2.
- Ability to understand and sign informed consent and HIPAA documents.
- Archival tumor biospecimen available for evaluation or treated on study if unavailable.
- Normal organ and marrow function defined by specific blood counts and liver/kidney function thresholds.
You will not qualify if you...
- Prior treatment with monomethyl auristatin E (MMAE)-based antibody-drug conjugates for urothelial cancer.
- Grade 2 or higher baseline sensory or motor neuropathy.
- Uncontrolled diabetes with HbA1c above 8%.
- Uncontrolled and untreated central nervous system metastases; stable CNS metastases allowed under conditions.
- Uncontrolled intercurrent illnesses including active infections, symptomatic heart failure or arrhythmia, or psychiatric/social impairments.
- History of another invasive malignancy within 3 years requiring treatment or residual disease.
- Active systemic antimicrobial treatment at first dose.
- Known HIV-positive on combination antiretroviral therapy.
- History of significant lung diseases or active pneumonitis.
- Prior allogeneic stem cell or solid organ transplant.
- Other medical or psychiatric conditions impairing study compliance.
- Active tuberculosis.
- Pregnant or breastfeeding.
- Active autoimmune diseases requiring systemic treatment in past 2 years, with some exceptions.
- High-dose steroids above 10 mg prednisone equivalent at enrollment.
- Prior immunotherapy for metastatic urothelial carcinoma causing severe adverse events requiring cessation.
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 - Approximately 18 weeks
Participants receive induction therapy with enfortumab vedotin plus pembrolizumab for 6 cycles over approximately 18 weeks. Enfortumab vedotin is administered intravenously on Days 1 and 8 of each 21-day cycle, and pembrolizumab is given intravenously on Day 1 of each cycle. Radiographic assessments occur after 3 cycles and after 6 cycles to evaluate response.
6 treatment cycles with multiple IV infusions and 2 radiographic assessments
Duration - Up to 2 years
Participants who achieve complete or partial response transition to pembrolizumab maintenance therapy. Pembrolizumab is given intravenously every 3 weeks or every 6 weeks for up to 2 years, depending on physician preference. Radiographic assessments occur every 12 weeks during maintenance. Treatment continues until disease progression, unacceptable toxicity, or completion of maintenance therapy.
IV infusions every 3 or 6 weeks and radiographic assessments every 12 weeks
Duration - Variable, up to study completion
Participants enter survival or long-term follow-up after progression, toxicity requiring treatment cessation, or early discontinuation of therapy. Follow-up includes monitoring for disease status and safety until progression or death.
Visits as needed for monitoring during follow-up
Trial Site Locations
Total: 1 location
1
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Actively Recruiting
Research Team
R
Ryan Romasko, MBA
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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