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Brief Title: Study of Sitravatinib + PD-(L)1 Checkpoint Inhibitor Regimens in 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

INTRODUCTION

  • Org Study ID: 516-003
  • Secondary ID: N/A
  • NTC ID: NCT03606174
  • Sponsor: 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.

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

PRIMARY OUTCOMES

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

Primary Outcome 1 - Timeframe: 36 months

CONDITION

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

ELIGIBILITY

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

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: Hirak Der-Torossian, MD

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

Email: miratistudylocator@emergingmed.com

LOCATION

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

Facility: University of California Irvine
Irvine, California 92868
United States
Status: Recruiting Contact: Contact
Mailinh Le

Facility: Rocky Mountain Cancer Centers
Aurora, Colorado 80012
United States
Status: Recruiting Contact: Contact
Patrick Ssebikejje

Facility: Yale School of Medicine
New Haven, Connecticut 06510
United States
Status: Recruiting Contact: Contact
Shelby DeCarlo

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

Facility: Moffitt Cancer Center
Tampa, Florida 33612
United States
Status: Recruiting Contact: Contact
Austin Lannon

Facility: SCRI - Florida Cancer Specialists - West Palm Beach
West Palm Beach, Florida 33401
United States
Status: Recruiting Contact: Contact
Naomi England

Facility: The University of Chicago
Chicago, Illinois 60637
United States
Status: Recruiting Contact: Contact
Briana Harrison

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

Facility: Norton Cancer Institute - Broadway
Louisville, Kentucky 40202
United States
Status: Recruiting Contact: Contact
Andrea Spencer

Facility: Maryland Oncology Hematology, P.A.
Lanham, Maryland 20706
United States
Status: Recruiting Contact: Contact
Meredith Flynn

Facility: Dana Farber Cancer Institute
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: Contact
Brenda Dickow

Facility: Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Status: Recruiting Contact: Contact
Jennifer Dill

Facility: Washington University School of Medicine - Siteman Cancer Center
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: Contact
Laura Frank

Facility: GU Research Network/Urology Cancer Center
Omaha, Nebraska 68130
United States
Status: Recruiting Contact: Contact
Christina Shirley

Facility: Comprehensive Cancer Centers of Nevada - Southwest
Las Vegas, Nevada 89169
United States
Status: Recruiting Contact: Contact
Rachel Page

Facility: New York Oncology Hematology - Albany Medical Center
Albany, New York 12206
United States
Status: Recruiting Contact: Contact
Jessica Doersam

Facility: Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Status: Recruiting Contact: Contact
Jessica Chaisson

Facility: Northwell Health Monter Cancer Center
Lake Success, New York 11042
United States
Status: Recruiting Contact: Contact
Vanessa Peters

Facility: NYU Langone Laura & Isaac Perlmutter Cancer Center
New York, New York 10016
United States
Status: Recruiting Contact: Contact
Rachel Munoz

Facility: Memorial Sloan-Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Contact
Julia Hurrelbrink

Facility: University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
United States
Status: Recruiting Contact: Contact
Shireen Desai

Facility: Duke University Hospital
Durham, North Carolina 27710
United States
Status: Recruiting Contact: Contact
Megan Buss

Facility: The Ohio State University College of Medicine
Columbus, Ohio 43202
United States
Status: Recruiting Contact: Contact
Matthew Fister

Facility: Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
United States
Status: Recruiting Contact: Contact
Francisca Fernandez

Facility: Vanderbilt University - Ingram Cancer Center
Nashville, Tennessee 37232
United States
Status: Recruiting Contact: Contact
Hina Nazir

Facility: Texas Oncology-Austin Central
Austin, Texas 78731
United States
Status: Recruiting Contact: Contact
Rudy Hernandez

Facility: Texas Oncology- Memorial City
Houston, Texas 77024
United States
Status: Recruiting Contact: Contact
Kim Chadwick

Facility: University of Texas - MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Claudia Phillips

Facility: Texas Oncology - Tyler
Tyler, Texas 75702
United States
Status: Recruiting Contact: Contact
Karen McClain

Facility: Virginia Cancer Specialists- Fairfax
Fairfax, Virginia 22031
United States
Status: Recruiting Contact: Contact
Colin Sievers

Facility: Virginia Oncology Associates
Norfolk, Virginia 23502
United States
Status: Recruiting Contact: N/A
Facility: Seattle Cancer Center Alliance
Seattle, Washington 98109
United States
Status: Recruiting Contact: N/A