A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma
NCT ID: NCT03606174
Last Updated: 2023-08-24
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
260 participants
INTERVENTIONAL
2018-09-11
2022-08-22
Brief Summary
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Detailed Description
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Pembrolizumab is a humanized IgG4 monoclonal antibody that binds to the PD-1 receptor and selectively blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Enfortumab vedotin (enfortumab) is an investigational ADC that is comprised of a fully human anti-Nectin-4 IgG1 monoclonal antibody conjugated to MMAE via a protease-cleavable linker. Enfortumab binds to cells that express Nectin-4 with high affinity, triggering the internalization and release of MMAE in target cells, inducing cell cycle arrest and apoptotic cell death. Early efficacy results from enfortumab in combination with pembrolizumab in frontline cisplatin-ineligible urothelial carcinoma in the ongoing EV-103 study have demonstrated encouraging activity with a safety profile that appears manageable and tolerable. Addition of sitravatinib to this combination might further augment clinical activity by selectively inhibiting key molecular and cellular pathways strongly implicated in checkpoint inhibitor resistance.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1
Patients previously treated with checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 2
Patients previously treated with checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 3
Patients previously treated with selected immunotherapies and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 4
Patients previously treated with with selected immunotherapies, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 5
Patients previously treated with platinum-based chemotherapy, but never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 6
Patients ineligible for treatment with platinum-based chemotherapy and never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 7
Patients previously treated with antibody-drug conjugate, checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 8
Patients previously treated with antibody-drug conjugate and checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 9
Patients previously treated with checkpoint inhibitor and platinum-based chemotherapy. There are 2 parts to this Cohort - a lead-in dose escalation portion and a dose expansion portion. In the dose escalation portion, treatment with up to 3 dose levels of sitravatinib in combination with up to 2 dose levels of pembrolizumab and enfortumab combination regimen to determine the recommended doses to be used in the combination treatment regimen and those doses will be further studied in the dose expansion portion. Pembrolizumab 200 mg over 30 min IV infusion every 3 weeks, sitravatinib orally once per day continuously in 21-day cycles (at 35 mg, 50 mg, 70 mg, or 100 mg) and enfortumab vedotin over 30 min IV infusion on Day 1 and Day 8 in 21-day cycles (at 1 mg/kg or 1.25 mg/kg).
Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Pembrolizumab
Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody
Enfortumab vedotin
Enfortumab is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a monoclonal antibody conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE)
Interventions
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Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Pembrolizumab
Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody
Enfortumab vedotin
Enfortumab is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a monoclonal antibody conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Adequate bone marrow and organ function
Exclusion Criteria
* Unacceptable toxicity with prior checkpoint inhibitor
* Impaired heart function
18 Years
ALL
No
Sponsors
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Mirati Therapeutics Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Hirak Der-Torossian, MD
Role: STUDY_DIRECTOR
Mirati Therapeutics Inc.
Locations
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The University of Arizona Cancer Center
Tucson, Arizona, United States
University of California Irvine
Irvine, California, United States
Rocky Mountain Cancer Centers
Aurora, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
SCRI - Florida Cancer Specialists- North Region
St. Petersburg, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
SCRI - Florida Cancer Specialists - West Palm Beach
West Palm Beach, Florida, United States
The University of Chicago
Chicago, Illinois, United States
Indiana University - Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
Norton Cancer Institute - Broadway
Louisville, Kentucky, United States
Ochsner Cancer Institute
New Orleans, Louisiana, United States
Maryland Oncology Hematology, P.A.
Lanham, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, United States
GU Research Network/Urology Cancer Center
Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada - Southwest
Las Vegas, Nevada, United States
New York Oncology Hematology - Albany Medical Center
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Northwell Health Monter Cancer Center
Lake Success, New York, United States
NYU Langone Laura & Isaac Perlmutter Cancer Center
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
New York-Presbyterian - Weill Cornell Medical Center
New York, New York, United States
University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Hospital
Durham, North Carolina, United States
The Ohio State University College of Medicine
Columbus, Ohio, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Vanderbilt University - Ingram Cancer Center
Nashville, Tennessee, United States
Texas Oncology-Austin Central
Austin, Texas, United States
Texas Oncology- Memorial City
Houston, Texas, United States
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States
University of Texas Health Science Center
San Antonio, Texas, United States
Texas Oncology - Tyler
Tyler, Texas, United States
Virginia Cancer Specialists- Fairfax
Fairfax, Virginia, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Seattle Cancer Center Alliance
Seattle, Washington, United States
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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516-003
Identifier Type: -
Identifier Source: org_study_id
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