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Clinical Trial 20507

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT04223856

Phase: Phase III
Prinicipal Investigator: Rohit Jain

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Study Title

An Open-Label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination with Pembrolizumab with or without Chemotherapy, versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer


This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together alone or with platinum chemotherapy 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.


Primary Objective: 1. To compare progression free survival (PFS) between experimental arms (enfortumab vedotin + pembrolizumab [Arm A] and enfortumab vedotin + pembrolizumab + cisplatin or carboplatin [Arm C]) and the control arm (gemcitabine + cisplatin or carboplatin [Arm B]) by blinded independent central review (BICR) 2. To compare overall survival (OS) between experimental arms (Arm A and Arm C) and the control arm (Arm B)




Enfortumab Vedotin (Padcev); Gemzar (gemcitabine); Paraplatin (carboplatin); Pembrolizumab (Keytruda); carboplatin (); cisplatin (); gemcitabine ()

Inclusion Criteria

  • 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 judgement
  • 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

  • Exclusion Criteria

  • 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 history of 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 3 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

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.