Condition: Metastatic Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03547973

Sponsor: Gilead Sciences

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Key Inclusion Criteria:

• Participants with histologically confirmed urothelial cancer (UC).
• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
• Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
• Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
• Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
• Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
• Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
• Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
• Cohorts 4 and 5: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).
• Adequate renal and hepatic function.
• Adequate hematologic parameters without transfusional support.
• Individuals must have a 3-month life expectancy.
• Have measurable disease by Computed Tomography Imaging (CT) or Magnetic Resonance Imaging (MRI) as per RECIST 1.1 criteria.

Key Exclusion Criteria:

• Females who are pregnant or lactating.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
• Has an active second malignancy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has known active Hepatitis B or Hepatitis C
• Has other concurrent medical or psychiatric conditions
• Cohorts 3 to 5: Has active autoimmune disease requiring systemic treatment with steroids or other immunosuppressive agent or any condition that in the Investigator's judgment precludes treatment with pembrolizumab, has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis, has received anti-PD-1/PD-L1 therapy previously
• Cohorts 4 and 5: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting. Note: Other protocol defined Inclusion/

Exclusion Criteria:

1. may apply.

View trial on ClinicalTrials.gov