Clinical Trials /

Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer

NCT03547973

Description:

This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen or anti-PD-1 /PD-L1 based immunotherapy. At least 321 patients are anticipated to be enrolled across approximately 40 sites from North America and Europe.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer
  • Official Title: Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy

Clinical Trial IDs

  • ORG STUDY ID: IMMU-132-06 - TROPHY U-01
  • NCT ID: NCT03547973

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
Sacituzumab govitecanIMMU-132Cohort 1 and Cohort 2

Purpose

This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen or anti-PD-1 /PD-L1 based immunotherapy. At least 321 patients are anticipated to be enrolled across approximately 40 sites from North America and Europe.

Detailed Description

      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.

      Cohort 4:

        -  DOR, CBR, and PFS based on central review by RECIST 1.1 criteria

        -  ORR, DOR, CBR, PFS based on investigator review by RECIST 1.1 criteria

        -  OS

        -  Safety and tolerability of sacituzumab govitecan in combination with cisplatin

      Cohort 5:

        -  DOR, CBR, and PFS based on central review by RECIST 1.1 criteria

        -  ORR, DOR, CBR, and PFS based on investigator review by RECIST 1.1 criteria

        -  OS

        -  Safety and tolerability of sacituzumab govitecan in combination with cisplatin and
           avelumab
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 and Cohort 2ExperimentalAll subjects will receive sacituzumab govitecan (IMMU-132) 10 mg/kg intravenously on Days 1 and 8 of a 21 day cycle. Cohort 1: Subjects with urothelial cancers, after platinum-based regimen (cisplatin or carboplatin) and anti-PD-1/anti-PD-L1 based therapy. Cohort 2: Subjects in second line therapy of urothelial cancers, ineligible for platinum-based therapy and anti-PD-1/anti-PD-L1 based therapies failure.
  • Sacituzumab govitecan
Cohort 3ExperimentalAll subjects in Cohort 3 will receive sacituzumab govitecan (IMMU-132) 10 mg/kg intravenously 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. Subjects who have had progression or recurrence of urothelial cancer following a platinum-containing regimen in the metastatic setting, or progression or recurrence of urothelial cancer within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
    Cohort 4ExperimentalAll subjects will first receive cisplatin (either at 70 mg/m2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) followed by sacituzumab govitecan on Days 1 and 8 of a 21-day cycle for up to 6 cycles. If premature termination of 1 agent occurs due to toxicity the other agent may be continued to complete up to 6 cycles of therapy. For subjects who have not progressed, maintenance therapy will begin with infusions of avelumab (800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks thereafter) followed by sacituzumab govitecan on Days 1 and 8 every 21 days.
      Cohort 5ExperimentalAll subjects will first receive cisplatin (either at 70 mg/m2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2), followed by sacituzumab govitecan on Days 1 and 8 of a 21-day cycle, and avelumab (800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks thereafter) for up to 6 cycles. If premature termination of 1 agent occurs due to toxicity the other agents may be continued to complete up to 6 cycles of therapy. For subjects who have not progressed, maintenance therapy will begin with 800 mg of avelumab every 2 weeks followed by infusions of sacituzumab govitecan on Days 1 and 8 every 21 days.

        Eligibility Criteria

                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.
              
        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:All
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Overall Response Rate (ORR)
        Time Frame:2 years
        Safety Issue:
        Description:ORR will be defined as the rate of the confirmed overall best response, Complete Remission (CR) or Partial Response (PR) and will be centrally reviewed based on Recist 1.1 by an independent centralized group of radiology experts.

        Secondary Outcome Measures

        Measure:Duration of Response (DOR)
        Time Frame:2 years
        Safety Issue:
        Description:DOR will be calculated from the date of the first evaluation showing documented response, PR, or CR, to the date of the first disease progression and will be centrally reviewed by an independent centralized group of radiology experts by response evaluation criteria in solid tumors (RECIST) 1.1 criteria and by immune-based therapeutics (iRECIST) criteria for Cohort 3 only.
        Measure:Progression-Free Survival (PFS)
        Time Frame:2 years
        Safety Issue:
        Description:PFS is defined as the time interval from the first dose start date to the date of disease progression and will be centrally reviewed by an independent centralized group of radiology experts by response evaluation criteria in solid tumors (RECIST) 1.1 criteria and by immune-based therapetics (iRECIST) criteria for Cohort 3 only.
        Measure:Overall Survival (OS)
        Time Frame:2 years
        Safety Issue:
        Description:OS will be measured from the date of first dose to death from any cause.
        Measure:Clinical Benefit Rate (CBR) (Cohort 3, 4 & 5)
        Time Frame:2 years
        Safety Issue:
        Description:CBR is defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) for at least 6 months.

        Details

        Phase:Phase 2
        Primary Purpose:Interventional
        Overall Status:Recruiting
        Lead Sponsor:Immunomedics, Inc.

        Last Updated

        February 16, 2021