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

Trial Status: Active

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.

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 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

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 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


City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Kathryn Hilburn
Phone: 310-633-8400
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Contact: Dorothy Chang
Phone: 714-509-2199


University of Colorado Hospital
Status: ACTIVE

District of Columbia

MedStar Georgetown University Hospital
Status: ACTIVE


Moffitt Cancer Center


Emory University Hospital / Winship Cancer Institute
Status: ACTIVE


Northwestern University


Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE

New York

New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Gopakumar V. Iyer
Phone: 646-888-4737

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Wake Forest University Health Sciences


Case Comprehensive Cancer Center
Ohio State University Comprehensive Cancer Center


University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE


UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Contact: Sonia Lisa Creighton
Phone: 210-450-1366


Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE


University of Virginia Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE


University of Wisconsin Hospital and Clinics

This study is being conducted to evaluate the combination of enfortumab vedotin +

pembrolizumab versus standard of care gemcitabine + platinum-containing chemotherapy, in

subjects with previously untreated locally advanced or metastatic urothelial cancer.

Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol

defined reason for study discontinuation occurs. Pembrolizumab may be administered for a

maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever

is first. Cisplatin or carboplatin plus gemcitabine may be administered for a maximum of 6

cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Astellas Pharma Global Development, Inc.

  • Primary ID SGN22E-003
  • Secondary IDs NCI-2020-01070, 2019-004542-15, MK-3475-A39, KEYNOTE KN-A39
  • ID NCT04223856