Skip to main content

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

Trial Status: Active

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 / gastroesophageal junction cancer / lower esophageal cancer (GC / GEJC / LEC), 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. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Subjects enrolled in the SAC cohorts and SAA cohort may receive combination treatment with both cabozantinib and atezolizumab after they experience radiographic progressive disease per the Investigator per RECIST 1.1. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

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/LEC, 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, 9, 11, 17, 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 (>10 mg daily prednisone equivalent) 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.

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Contact: Xiomara Menendez
Phone: 323-717-7708
Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
San Diego
University of California San Diego
Status: ACTIVE

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

New Jersey

New Brunswick
Rutgers Cancer Institute of New Jersey
Status: ACTIVE

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: ACTIVE
New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: IN_REVIEW
Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: systems coordinator
Phone: 215-214-1558
Thomas Jefferson University Hospital
Status: ACTIVE

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
Houston
M D Anderson Cancer Center
Status: ACTIVE
San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: ACTIVE
Contact: Sonia Lisa Creighton
Phone: 210-450-1366

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Virginia

Charlottesville
University of Virginia Cancer Center
Status: ACTIVE

- 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/LEC, CRC, H&N, and DTC. - Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent cabozantinib in UC, NSCLC, and CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy - Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent atezolizumab in CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Exelixis Inc

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