Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03547973

Sponsor: Immunomedics, Inc.

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Patients with histologically confirmed urothelial cancer.
• 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): 1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease; 2. 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-PD-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. Subject 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. Cohort 4 and 5: Subject has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Cohort 4 and 5: Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For subjects receiving cisplatin at 70 mg/m2 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. Subjects with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m2 Day 1 and Day 8 of every 21-day cycle).
• Adequate renal and hepatic function.
• Adequate hematologic parameters without transfusional support.
• Creatinine clearance ≥30mL/min as calculated by the Cockroft-Gault formula.
• Subjects must have a 3-month life expectancy.
• Have measurable disease by CT or MRI as per RECIST 1.1 criteria.

Exclusion Criteria:

• Women 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
• Cohort 3: 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
• Cohort 3: Has received a live vaccine within 30 days prior to the first dose of study drug(s)
• Cohort 3: Has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis
• Cohort 3: Has received anti-PD-1/PD-L1 therapy previously Cohort 4 and 5: Refractory to platinum (i.e., relapsed ≤12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.

View trial on ClinicalTrials.gov