Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

Running, not enrolling · Phase 3

Conditions studied: Urothelial Cancer

In brief

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

Key facts

Study ID

NCT04223856

Run by

Astellas Pharma Global Development, Inc.

People needed

886

Starts

2020-03-30

Expected to finish

2028-03-01

Last updated by the study team

2026-05-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
• Measurable disease by investigator assessment according to RECIST v1.1
• Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
• Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
• Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
• Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
• Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
• Adequate hematologic and organ function

You may not qualify if…

• Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
• Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
• Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
• Uncontrolled diabetes
• Estimated life expectancy of less than 12 weeks
• Active central nervous system (CNS) metastases
• Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
• Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
• Receipt of radiotherapy within 2 weeks prior to randomization
• Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
• Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplant
• Received a live attenuated vaccine within 30 days prior to randomization

Where it is running

• Arizona Oncology Associates PD - HOPE — Tucson, Arizona, United States
• Providence St Joseph Medical Center — Burbank, California, United States
• City of Hope National Medical Center — Duarte, California, United States
• University of California Los Angeles Medical Center — Los Angeles, California, United States
• University of California Irvine - Newport — Orange, California, United States
• Rocky Mountain Cancer Centers - Aurora — Aurora, Colorado, United States
• University of Colorado Hospital / University of Colorado — Aurora, Colorado, United States
• Cancer Centers of Colorado - Denver — Denver, Colorado, United States
• Yale Cancer Center — New Haven, Connecticut, United States
• Eastern CT Hematology and Oncology Associates — Norwich, Connecticut, United States
• Lombardi Cancer Center / Georgetown University Medical Center — Washington D.C., District of Columbia, United States
• H. Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• Winship Cancer Institute / Emory University School of Medicine — Atlanta, Georgia, United States
• Georgia Cancer Specialists / Northside Hospital Cancer Institute — Marietta, Georgia, United States
• Louisiana State University/ East Jefferson General Hospital — Metairie, Louisiana, United States
• Maine Health Cancer Care — Biddeford, Maine, United States
• Johns Hopkins Medical Center — Baltimore, Maryland, United States
• Comprehensive Cancer Centers of Nevada — Las Vegas, Nevada, United States
• New Mexico Cancer Center — Albuquerque, New Mexico, United States
• New York University (NYU) Cancer Institute — New York, New York, United States
• Mount Sinai Medical Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Vidant Medical Center — Greenville, North Carolina, United States
• The Cleveland Clinic — Cleveland, Ohio, United States
• Ironwood Cancer & Research Centers - Chandler — Chandler, Arizona, United States

Full record on ClinicalTrials.gov

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