A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors


Condition: Urothelial Carcinoma, Renal Cell Carcinoma, Non-Small Cell Lung Cancer, Castration-resistant Prostate Cancer, Triple Negative Breast Cancer, Ovarian Cancer, Endometrial Cancer, Hepatocellular Carcinoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Colorectal Cancer, Head and Neck Cancer, Differentiated Thyroid Cancer

Intervention:

  • Drug: cabozantinib
  • Drug: atezolizumab
  • Drug: cabozantinib
  • Drug: cabozantinib

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03170960

Sponsor: Exelixis

Primary Outcome Measures:

  • Measure: Dose Escalation: MTD/Recommended Dose
  • Time Frame: Up to 6 months
  • Safety Issue:
  • Measure: Dose Expansion: ORR
  • Time Frame: Up to 31 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Incidence and severity of nonserious AEs and SAEs (Safety)
  • Time Frame: Up to 41 months
  • Safety Issue:

Estimated Enrollment: 1000

Study Start Date: September 5, 2017

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. 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) 2. Measurable disease per RECIST 1.1 as determined by the investigator. 3. Tumor tissue material available (archival or recent tumor biopsy) 4. 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. 5. Age eighteen years or older on the day of consent. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7. Adequate organ and marrow function. 8. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception. 9. Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria:

  1. 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
  2. Other restrictions regarding prior therapy may apply.
  3. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.
  4. Concomitant anticoagulation with oral anticoagulants.
  5. Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
  6. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
  7. 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).
  8. Pregnant or lactating females.
  9. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  10. Diagnosis of another malignancy within 2 years before first dose of study treatment.

Contact:

  • Exelixis Clinical Trials
  • 1-888-EXELIXIS (888-393-5494)

Locations:

  • Exelixis Clinical Site #18
  • Phoenix Arizona 85054 United States
  • Exelixis Clinical Site #1
  • Duarte California 91010 United States
  • Exelixis Clinical Site #20
  • La Jolla California 92090 United States
  • Exelixis Clinical Site #21
  • Stanford California 94305 United States
  • Exelixis Clinical Site #16
  • Jacksonville Florida 32224 United States
  • Exelixis Clinical Site #23
  • Fairway Kansas 66205 United States
  • Exelixis Clinical Site #24
  • New Orleans Louisiana 70112 United States
  • Exelixis Clinical Site #10
  • Boston Massachusetts 02215 United States
  • Exelixis Clinical Site #3
  • Detroit Michigan 48201 United States
  • Exelixis Clinical Site #17
  • Rochester Minnesota 55905 United States
  • Exelixis Clinical Site #27
  • East Brunswick New Jersey 08816 United States
  • Exelixis Clinical Site #11
  • New York New York 10029 United States
  • Exelixis Clinical Site #6
  • Oklahoma City Oklahoma 73120 United States
  • Exelixis Clinical Site #15
  • Philadelphia Pennsylvania 19107 United States
  • Exelixis Clinical Site #13
  • Dallas Texas 75246 United States
  • Exelixis Clinical Site #26
  • Dallas Texas 75390 United States
  • Exelixis Clinical Site #2
  • Salt Lake City Utah 84112 United States
  • Exelixis Clinical Site #14
  • Charlottesville Virginia 22908 United States
  • Exelixis Clinical Site #8
  • Villejuif Cedex 94805 France
  • Exelixis Clinical Site #7
  • Paris 75010 France
  • Exelixis Clinical Site #25
  • Milano 20133 Italy
  • Exelixis Clinical Site #4
  • Milano 20133 Italy
  • Exelixis Clinical Site #12
  • Nijmegen Gelderland 6525 GA Netherlands
  • Exelixis Clinical Site #9
  • Barcelona 08035 Spain
  • Exelixis Clinical Site #22
  • Madrid 28041 Spain
  • Exelixis Clinical Site #5
  • Madrid 28041 Spain
  • Exelixis Clinical Site #19
  • London EC1M 6BQ United Kingdom

View trial on ClinicalTrials.gov


E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe