Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer
- 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):
- 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-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.
- 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.
- 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
Salt Lake City
This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen and/or anti-PD-1 / PD-L1 based immunotherapy. The primary objective is Objective Response Rate (ORR) based on central review. The secondary objectives for Cohorts 1 and 2 are Duration of Response (DOR) and Progression Free Survival (PFS) both based on central review and Overall Survival (OS). The secondary objectives for Cohort 3 are Duration of Response (DOR),Clinical Benefit Rate (CBR), and Progression Free Survival (PFS) based on central review by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; Duration of Response (DOR),Clinical Benefit Rate (CBR), and Progression Free Survival (PFS) based on central review for Immune-based therapeutics (iRECIST) criteria, Overall Survival (OS), safety and tolerability of IMMU-132 in combination with pembrolizumab. Subjects will receive IMMU-132 10 mg/kg administered intravenously on Days 1 and 8 of a 21-day cycle to be continued in the absence of unacceptable toxicity or disease progression. In Cohort 3, all subjects will first receive IMMU-132 on Days 1 and 8 of a 21-day cycle followed by pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle. After discontinuation of treatment, patients will have a 30-day safety follow-up after last dose and then will be followed every 12 weeks for survival for a maximum of 2 years.
Trial Phase Phase II
Trial Type Treatment
- Primary ID IMMU-132-06 - TROPHY U-01
- Secondary IDs NCI-2018-03421
- Clinicaltrials.gov ID NCT03547973