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

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ClinicalTrials.gov Identifier: NCT03547973
Recruitment Status : Recruiting
First Posted : June 6, 2018
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Sacituzumab govitecan Combination Product: Sacituzumab govitecan and pembrolizumab Combination Product: IMMU-132 AND cisplatin Combination Product: IMMU-132 and cisplatin and avelumab Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 321 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 31, 2018
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1 and Cohort 2

All 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.

Drug: Sacituzumab govitecan
All subjects will receive sacituzumab govitecan (IMMU-132) 10 mg/kg intravenously on Days 1 and 8 of a 21 day cycle.
Other Name: IMMU-132

Experimental: Cohort 3

All 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.

Combination Product: Sacituzumab govitecan and pembrolizumab
All subjects will first 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.
Other Name: IMMU-132 and pembrolizumab

Experimental: Cohort 4
All 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.
Combination Product: IMMU-132 AND cisplatin
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

Experimental: Cohort 5
All 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.
Combination Product: IMMU-132 and cisplatin and avelumab
all 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




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 2 years ]
    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 :
  1. Duration of Response (DOR) [ Time Frame: 2 years ]
    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.

  2. Progression-Free Survival (PFS) [ Time Frame: 2 years ]
    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.

  3. Overall Survival (OS) [ Time Frame: 2 years ]
    OS will be measured from the date of first dose to death from any cause.

  4. Clinical Benefit Rate (CBR) (Cohort 3, 4 & 5) [ Time Frame: 2 years ]
    CBR is defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) for at least 6 months.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03547973


Contacts
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Contact: Addie Ruffins 8622603585 aruffins@immunomedics.com
Contact: John Benedetto jbenedetto@Immunomedics.com

Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Trishna Goswami, MD Gilead Sciences
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03547973    
Other Study ID Numbers: IMMU-132-06 - TROPHY U-01
First Posted: June 6, 2018    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cisplatin
Pembrolizumab
Camptothecin
Immunoconjugates
Antineoplastic Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs