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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
therapy.

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

Condition:

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

Eligibility

Criteria:
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)

Email: miratistudylocator@emergingmed.com

Locations

Facility Status Contact
The University of Arizona Cancer Center
Tucson, Arizona 85724
United States
Recruiting Ava Wong

University of California Irvine
Irvine, California 92868
United States
Recruiting Mailinh Le

Rocky Mountain Cancer Centers
Aurora, Colorado 80012
United States
Recruiting Patrick Ssebikejje

Yale School of Medicine
New Haven, Connecticut 06510
United States
Recruiting Shelby DeCarlo

SCRI - Florida Cancer Specialists- North Region
Saint Petersburg, Florida 33705
United States
Recruiting Catherine McQuade

Moffitt Cancer Center
Tampa, Florida 33612
United States
Recruiting Austin Lannon

SCRI - Florida Cancer Specialists - West Palm Beach
West Palm Beach, Florida 33401
United States
Recruiting Naomi England

The University of Chicago
Chicago, Illinois 60637
United States
Recruiting Briana Harrison

Indiana University - Melvin & Bren Simon Cancer Center
Indianapolis, Indiana 46202
United States
Recruiting Nick Patel

Norton Cancer Institute - Broadway
Louisville, Kentucky 40202
United States
Recruiting Andrea Spencer

Ochsner Cancer Institute
New Orleans, Louisiana 70121
United States
Completed
Maryland Oncology Hematology, P.A.
Lanham, Maryland 20706
United States
Recruiting Margaret Johannesen

Dana Farber Cancer Institute
Boston, Massachusetts 02215
United States
Recruiting Meredith Flynn

Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Recruiting Brenda Dickow

Washington University School of Medicine - Siteman Cancer Center
Saint Louis, Missouri 63110
United States
Recruiting Jennifer Dill

GU Research Network/Urology Cancer Center
Omaha, Nebraska 68130
United States
Recruiting Laura Frank

Comprehensive Cancer Centers of Nevada - Southwest
Las Vegas, Nevada 89169
United States
Recruiting Christina Shirley

New York Oncology Hematology - Albany Medical Center
Albany, New York 12206
United States
Recruiting Rachel Page

Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting Jessica Doersam

Northwell Health Monter Cancer Center
Lake Success, New York 11042
United States
Recruiting
NYU Langone Laura & Isaac Perlmutter Cancer Center
New York, New York 10016
United States
Recruiting Jessica Chaisson

Memorial Sloan-Kettering Cancer Center
New York, New York 10065
United States
Recruiting Vanessa Peters

University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
United States
Recruiting Rachel Munoz

Duke University Hospital
Durham, North Carolina 27710
United States
Recruiting Julia Hurrelbrink

The Ohio State University College of Medicine
Columbus, Ohio 43202
United States
Recruiting Shireen Desai

Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
United States
Recruiting Megan Buss

Vanderbilt University - Ingram Cancer Center
Nashville, Tennessee 37232
United States
Recruiting Matthew Fister

Texas Oncology-Austin Central
Austin, Texas 78731
United States
Recruiting Francisca Fernandez

Texas Oncology- Memorial City
Houston, Texas 77024
United States
Recruiting Hina Nazir

University of Texas - MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Rudy Hernandez

Texas Oncology - Tyler
Tyler, Texas 75702
United States
Recruiting Kim Chadwick

Virginia Cancer Specialists- Fairfax
Fairfax, Virginia 22031
United States
Recruiting Claudia Phillips

Virginia Oncology Associates
Norfolk, Virginia 23502
United States
Recruiting Karen McClain

Seattle Cancer Center Alliance
Seattle, Washington 98109
United States
Recruiting Colin Sievers