Back to Clinical Trials

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

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


  • Org Study ID: SGN22E-003
  • Secondary ID: N/A
  • NCT ID: NCT04223856
  • Sponsor: Astellas Pharma Global Development, Inc.


This clinical trial uses a drug called enfortumab vedotin. The Food and Drug Administration (FDA) has approved enfortumab vedotin for sale in the US. It’s approved for adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter, or urethra) that has been treated before and that has spread or cannot be removed by surgery. 

We are studying enfortumab vedotin to find out if it works for your type of cancer when given with other drugs. We want to see if this drug combination works better than the available approved treatments. We also want to learn more about the side effects. A side effect is anything the drug does to your body besides treating your disease. We don’t yet know if enfortumab vedotin works better or worse than other treatments when combined with other drugs. Learning how this drug combination works and about the side effects will help us understand if it works better or worse than other treatments.

The drug we are using in this study in combination with enfortumab vedotin is pembrolizumab (brand name KEYTRUDA®). Pembrolizumab is approved by the FDA to treat several types of cancer, including cancer of the urinary system, in some people. This clinical trial also uses chemotherapy drugs such as cisplatin, carboplatin, and gemcitabine. These chemotherapy drugs are approved by the FDA for treating various cancers.



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.

  • Overall Status
  • Start Date
    March 30, 2020
  • Phase
    Phase 3
  • Study Type


Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A


  • Urothelial Cancer


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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


Name: Zejing Wang, MD, PhD, John Lu, MD

Role: Study Director, Study Director

Affiliation: Seagen Inc., Seagen Inc.

Overall Contact

Name: Seagen Inc. Trial Information Support

Phone: 866-333-7436



Facility Status Contact