Brief Title
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
Official Title
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
Brief Summary
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.
Detailed Description
- 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
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Dose Escalation: MTD/Recommended Dose
Secondary Outcome
Incidence and severity of nonserious AEs and SAEs (Safety)
Condition
Urothelial Carcinoma
Intervention
cabozantinib
Study Arms / Comparison Groups
Dose Escalation
Description: Subjects will accrue in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg orally qd in combination with standard dosing regimen of atezolizumab (1200 mg infusion q3w). A standard "3 plus 3" design will be utilized to determine a recommended combination dosing regimen for the Expansion Stage.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1732
Start Date
September 5, 2017
Completion Date
December 2022
Primary Completion Date
December 2021
Eligibility 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 (>10 mg daily prednisone equivalent) 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 1-888-EXELIXIS (888-393-5494), [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03170960
Organization ID
XL184-021
Responsible Party
Sponsor
Study Sponsor
Exelixis
Study Sponsor
, ,
Verification Date
April 2021