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

Purpose

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.

Condition

  • Urothelial Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A
Enfortumab vedotin + pembrolizumab
  • Drug: Enfortumab vedotin
    Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle
    Other names:
    • ASG-22CE
    • ASG-22ME
    • PADCEV
  • Drug: Pembrolizumab
    IV infusion on Day 1 of every 3-week cycle
    Other names:
    • Keytruda
Active Comparator
Arm B
Gemcitabine + cisplatin or carboplatin
  • Drug: Cisplatin
    administered as IV infusion on Day 1 of each 3-week cycle
  • Drug: Carboplatin
    Dosed according to local guidelines and will be administered as IV infusion on Day 1 of each 3-week cycle
  • Drug: Gemcitabine
    IV infusion on Days 1 and 8 of every 3 week cycle
Experimental
Arm C (Not Recruiting)
Enfortumab vedotin + pembrolizumab + Cisplatin or carboplatin
  • Drug: Enfortumab vedotin
    Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle
    Other names:
    • ASG-22CE
    • ASG-22ME
    • PADCEV
  • Drug: Pembrolizumab
    IV infusion on Day 1 of every 3-week cycle
    Other names:
    • Keytruda
  • Drug: Cisplatin
    administered as IV infusion on Day 1 of each 3-week cycle
  • Drug: Carboplatin
    Dosed according to local guidelines and will be administered as IV infusion on Day 1 of each 3-week cycle

More Details

Status
Recruiting
Sponsor
Astellas Pharma Global Development, Inc.

Study Contact

Seagen Inc. Trial Information Support
866-333-7436
clinicaltrials@seagen.com

Detailed Description

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.