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. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.
- 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
- Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of
single-agent atezolizumab in CRPC subjects
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | September 5, 2017 | Phase 1/Phase 2 | Interventional |
Primary Outcome 1 - Measure: Dose Escalation: MTD/Recommended Dose
Primary Outcome 1 - Time Frame: Up to 6 months
Primary Outcome 2 - Measure: Dose Expansion: ORR
Primary Outcome 2 - Time Frame: Up to 31 months
Criteria:
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/LEC, 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, 9, 11, 17, 19 and 20. Other restrictions regarding prior therapy may apply.
2. Known brain metastases or cranial epidural disease unless adequately treated and
stable for at least 4 weeks before first dose of study treatment.
3. Concomitant anticoagulation with oral anticoagulants.
4. Subject is receiving systemic steroid therapy or any other form of immunosuppressive
therapy within 2 weeks prior to first dose of study treatment.
5. Administration of a live, attenuated vaccine within 30 days before first dose of study
treatment.
6. 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).
7. Pregnant or lactating females.
8. Previously identified allergy or hypersensitivity to components of the study treatment
formulations.
9. Diagnosis of another malignancy within 2 years before first dose of study treatment.
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Exelixis Clinical Trials
Phone: 1-888-EXELIXIS (888-393-5494)
Email: druginfo@exelixis.com
Facility | Status | Contact |
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Exelixis Clinical Site #53 Gilbert, Arizona 85234 United States |
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Exelixis Clinical Site #18 Phoenix, Arizona 85054 United States |
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Exelixis Clinical Site #1 Duarte, California 91010 United States |
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Exelixis Clinical Site #20 La Jolla, California 92090 United States |
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Exelixis Clinical Site #46 Los Angeles, California 90025 United States |
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Exelixis Clinical Site #51 Newport Beach, California 92663 United States |
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Exelixis Clinical Site #21 Stanford, California 94305 United States |
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Exelixis Clinical Site #34 Denver, Colorado 80218 United States |
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Exelixis Clinical Site #50 Denver, Colorado 80218 United States |
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Exelixis Clinical Site #42 New Haven, Connecticut 06511 United States |
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Exelixis Clinical Site #48 Washington, District of Columbia 20007 United States |
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Exelixis Clinical Site #16 Jacksonville, Florida 32224 United States |
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Exelixis Clinical Site #32 Harvey, Illinois 60426 United States |
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Exelixis Clinical Site #23 Fairway, Kansas 66205 United States |
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Exelixis Clinical Site #57 Lexington, Kentucky 40536 United States |
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Exelixis Clinical Site #24 New Orleans, Louisiana 70112 United States |
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Exelixis Clinical Site #10 Boston, Massachusetts 02215 United States |
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Exelixis Clinical Site #3 Detroit, Michigan 48201 United States |
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Exelixis Clinical Site #17 Rochester, Minnesota 55905 United States |
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Exelixis Clinical Site #43 Kansas City, Missouri 64111 United States |
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Exelixis Clinical Site #35 Omaha, Nebraska 68130 United States |
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Exelixis Clinical Site #38 Camden, New Jersey 08103 United States |
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Exelixis Clinical Site #27 East Brunswick, New Jersey 08816 United States |
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Exelixis Clinical Site #31 New Brunswick, New Jersey 08903 United States |
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Exelixis Clinical Site #37 Bronx, New York 10461 United States |
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Exelixis Clinical Site #40 East Setauket, New York 11733 United States |
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Exelixis Clinical Site #11 New York, New York 10029 United States |
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Exelixis Clinical Site #49 Columbus, Ohio 43210 United States |
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Exelixis Clinical Site #6 Oklahoma City, Oklahoma 73120 United States |
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Exelixis Clinical Site #45 Portland, Oregon 97239 United States |
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Exelixis Clinical Site #41 Bethlehem, Pennsylvania 18015 United States |
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Exelixis Clinical Site #15 Philadelphia, Pennsylvania 19107 United States |
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Exelixis Clinical Site #55 Philadelphia, Pennsylvania 19111 United States |
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Exelixis Clinical Site #13 Dallas, Texas 75246 United States |
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Exelixis Clinical Site #26 Dallas, Texas 75390 United States |
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Exelixis Clinical Site #29 Houston, Texas 77030 United States |
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Exelixis Clinical Site #39 Houston, Texas 77030 United States |
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Exelixis Clinical Site #44 Houston, Texas 77030 United States |
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Exelixis Clinical Site #33 Lubbock, Texas 79410 United States |
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Exelixis Clinical Site #2 Salt Lake City, Utah 84112 United States |
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Exelixis Clinical Site #30 Blacksburg, Virginia 24060 United States |
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Exelixis Clinical Site #14 Charlottesville, Virginia 22908 United States |
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Exelixis Clinical Site #52 Gent, 9000 Belgium |
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Exelixis Clinical Site #54 Leuven, 3000 Belgium |
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Exelixis Clinical Site #8 Villejuif, Cedex 94805 France |
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Exelixis Clinical Site #7 Paris, 75010 France |
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Exelixis Clinical Site #56 Düsseldorf, Nordrhein-Westfalen 40225 Germany |
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Exelixis Clinical Site #36 Tübingen, 72076 Germany |
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Exelixis Clinical Site #47 Rozzano, Milano 20089 Italy |
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Exelixis Clinical Site #25 Milano, 20133 Italy |
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Exelixis Clinical Site #4 Milano, 20133 Italy |
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Exelixis Clinical Site #12 Nijmegen, Gelderland 6525 GA Netherlands |
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Exelixis Clinical Site #28 Barcelona, 08035 Spain |
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Exelixis Clinical Site #9 Barcelona, 08035 Spain |
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Exelixis Clinical Site #22 Madrid, 28041 Spain |
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Exelixis Clinical Site #5 Madrid, 28041 Spain |
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Exelixis Clinical Site #19 London, EC1M 6BQ United Kingdom |
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