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Study of Sitravatinib and Nivolumab in Urothelial Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03606174
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
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Brief Summary:
The study will evaluate the clinical activity of nivolumab in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Urothelial Carcinoma Bladder Urothelial Carcinoma Ureter Urothelial Carcinoma of the Renal Pelvis and Ureter Urothelial Carcinoma Urethra Drug: Sitravatinib Drug: Nivolumab Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: There are 8 cohorts (having 9-45 maximum patients enrolled in each; based upon response rate and the predicted probability design). Patients are assigned to cohorts based upon their prior treatments for urothelial carcinoma. All patients receive the same treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients With Advanced or Metastatic Urothelial Carcinoma
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo
Experimental: 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.
 Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Name: MGCD516

Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Name: Opdivo


Outcome Measures
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Primary Outcome Measures :
  1. Number of patients experiencing tumor size reduction [ Time Frame: duration of study ]
    overall response rate by RECISTv1.1


Secondary Outcome Measures :
  1. Number of patients experiencing adverse events [ Time Frame: duration of study ]
    characterization of adverse events by incidence, severity, timing, seriousness & relationship to study treatment

  2. Blood plasma concentration of the investigational agent [ Time Frame: duration of study ]
    Blood plasma concentration of the investigational agent

  3. characterization of patients experiencing tumor size reduction [ Time Frame: 12 months ]
    duration of response, clinical benefit ratio, progressive free-survival, overall survival


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03606174


Contacts
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Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 (toll free) miratistudylocator@emergingmed.com

Locations
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Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Hirak Der-Torossian, MD Mirati Therapeutics Inc.
More Information
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Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03606174    
Other Study ID Numbers: 516-003
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: March 2, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirati Therapeutics Inc.:
MGCD516
Antineoplastic Agents
Immunologic Factors
Nivolumab
Tyrosine Kinase Inhibitor
 VEGFR
TAM RTKs
PD-1
PD-L1
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
 Urogenital Neoplasms
Neoplasms by Site
Urologic Diseases
Urinary Bladder Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents