Overview

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

Status:
Recruiting
Trial end date:
2023-11-30
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Astellas Pharma Global Development, Inc.
Collaborators:
Merck Sharp & Dohme Corp.
Seagen Inc.
Seattle Genetics, Inc.
Treatments:
Carboplatin
Cisplatin
Gemcitabine
Pembrolizumab
Criteria
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