An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)

  • End date
    Sep 30, 2027
  • participants needed
  • sponsor
    Astellas Pharma Global Development, Inc.
Updated on 24 October 2022
systemic therapy
measurable disease
adjuvant chemotherapy
transitional cell carcinoma
metastatic urothelial carcinoma
enfortumab vedotin


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.


Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

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.

Condition Urothelial Cancer
Treatment cisplatin, carboplatin, Gemcitabine, Pembrolizumab, Enfortumab vedotin
Clinical Study IdentifierNCT04223856
SponsorAstellas Pharma Global Development, Inc.
Last Modified on24 October 2022


Yes No Not Sure

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
Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
metastatic urothelial carcinoma with the following exceptions
Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
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
Must be considered eligible to receive cisplatin- or carboplatin-containing
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
chemotherapy, in the investigator's judgment
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
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
Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
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
Active keratitis or corneal ulcerations
History of autoimmune disease that has required systemic treatment in the past 2 years
Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
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
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