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BRIEF TITLE: Study of Sitravatinib in Combination With Nivolumab in Patients With Advanced or Metastatic Urothelial Carcinoma

A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma

  • Org Study ID: 516-003
  • Secondary ID:
  • NCT ID: NCT03606174
  • NCT Alias:
  • Sponsor: Mirati Therapeutics Inc. - Industry
  • Source: Mirati Therapeutics Inc.

Brief Summary

The study will evaluate the clinical activity of PD-(L)1 Checkpoint Inhibitor regimens in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.

Detailed Description

Sitravatinib is an orally-available, small molecule inhibitor of a closely related spectrum
of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family,
KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Nivolumab is a human IgG
monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its
interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1
pathway-mediated inhibition of the immune response including anti-tumor immune response.
Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune
modulatory and antitumor properties could enhance the antitumor efficacy observed with either
agent alone. Sitravatinib selectively inhibits key molecular and cellular pathways strongly
implicated in checkpoint inhibitor resistance and therefore represents a rational strategy to
enhance or restore anti-tumor immunity when combined with nivolumab, a checkpoint inhibitor

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.

Overal Status Start Date Phase Study Type
Recruiting September 11, 2018 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Objective Response Rate (ORR)

Primary Outcome 1 - Time Frame: 36 months


  • Urothelial Carcinoma
  • Urothelial Carcinoma Bladder
  • Urothelial Carcinoma Ureter
  • Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Urothelial Carcinoma Urethra


Inclusion Criteria:

- Diagnosis of urothelial carcinoma

- Adequate bone marrow and organ function

Exclusion Criteria:

- Uncontrolled tumor in the brain

- Unacceptable toxicity with prior checkpoint inhibitor

- Impaired heart function
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Hirak Der-Torossian, MD

Role: Study Director

Affiliation: Mirati Therapeutics Inc.

Overall Contact

Name: Mirati Therapeutics Study Locator Services

Phone: 1-844-893-5530 (toll free)



Facility Status Contact
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New Haven, Connecticut 06510
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SCRI - Florida Cancer Specialists- North Region
Saint Petersburg, Florida 33705
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Indiana University - Melvin & Bren Simon Cancer Center
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Norton Cancer Institute - Broadway
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Ochsner Cancer Institute
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Barbara Ann Karmanos Cancer Institute
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Washington University School of Medicine - Siteman Cancer Center
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GU Research Network/Urology Cancer Center
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Comprehensive Cancer Centers of Nevada - Southwest
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New York Oncology Hematology - Albany Medical Center
Albany, New York 12206
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Roswell Park Cancer Institute
Buffalo, New York 14263
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Northwell Health Monter Cancer Center
Lake Success, New York 11042
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Memorial Sloan-Kettering Cancer Center
New York, New York 10065
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University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
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Duke University Hospital
Durham, North Carolina 27710
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The Ohio State University College of Medicine
Columbus, Ohio 43202
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Allegheny General Hoospital
Pittsburgh, Pennsylvania 15212
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Vanderbilt University - Ingram Cancer Center
Nashville, Tennessee 37232
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Texas Oncology-Austin Central
Austin, Texas 78731
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Texas Oncology- Memorial City
Houston, Texas 77024
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University of Texas - MD Anderson Cancer Center
Houston, Texas 77030
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Texas Oncology - Tyler
Tyler, Texas 75702
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Virginia Cancer Specialists- Fairfax
Fairfax, Virginia 22031
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Virginia Oncology Associates
Norfolk, Virginia 23502
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