Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Status: Active

Description

This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer and gastroesophageal junction cancer (GC / GEJC), colorectal cancer (CRC), head and neck (H&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications. Two exploratory single-agent cabozantinib (SAC) cohorts will also be enrolled with UC or NSCLC subjects.

Eligibility Criteria

Inclusion Criteria

  • Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
  • Dose-Escalation Stage:
  • Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
  • Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy
  • Expansion Stage:
  • Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC, CRC, H&N cancer, and DTC as outlined above)
  • Measurable disease per RECIST 1.1 as determined by the investigator.
  • Tumor tissue material available (archival or recent tumor biopsy)
  • Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Age eighteen years or older on the day of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Adequate organ and marrow function.
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
  • Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria

  • Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5, 7,19 and 20. Other restrictions regarding prior therapy may apply.
  • Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.
  • Concomitant anticoagulation with oral anticoagulants.
  • Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
  • Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C).
  • Pregnant or lactating females.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment.

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Temporarily closed to accrual
Name Not Available

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: Active
Name Not Available

Florida

Jacksonville
Mayo Clinic in Florida
Status: Temporarily closed to accrual
Name Not Available

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Temporarily closed to accrual
Name Not Available

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: In review
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Name Not Available

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
Email: marcella.aguilar@utsouthwestern.edu
Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

- Dose Escalation Stage: to determine the schedule and maximum tolerated dose (MTD) and/or recommended Expansion Stage dose of cabozantinib when taken in combination with a standard dosing regimen of atezolizumab (1200 mg infusion, once every 3 weeks). - Expansion Stage: to determine the preliminary efficacy (objective response rate [ORR] per RECIST 1.1) and safety of the recommended combination dose of cabozantinib with atezolizumab in eighteen tumor-specific cohorts including subjects with advanced UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC, CRC, H&N, and DTC. - Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent cabozantinib in UC and NSCLC subjects

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Exelixis Inc

Trial IDs

Primary ID XL184-021
Secondary IDs NCI-2017-01455
Clinicaltrials.gov ID NCT03170960