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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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Washington University School of Medicine - Siteman Cancer Center
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New York Oncology Hematology - Albany Medical Center
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Roswell Park Cancer Institute
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Northwell Health Monter Cancer Center
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NYU Langone Laura & Isaac Perlmutter Cancer Center
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Memorial Sloan-Kettering Cancer Center
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University of North Carolina - Lineberger Comprehensive Cancer Center
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Duke University Hospital
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The Ohio State University College of Medicine
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Allegheny General Hospital
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Vanderbilt University - Ingram Cancer Center
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Texas Oncology-Austin Central
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Texas Oncology- Memorial City
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University of Texas - MD Anderson Cancer Center
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Texas Oncology - Tyler
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Virginia Cancer Specialists- Fairfax
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Virginia Oncology Associates
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Recruiting Karen McClain

Seattle Cancer Center Alliance
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Recruiting Colin Sievers