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

Not Recruiting

Trial ID: NCT03170960,


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.

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

Stanford Investigator(s)

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


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

   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

   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

   9. Diagnosis of another malignancy within 2 years before first dose of study treatment.


drug: cabozantinib

drug: atezolizumab

drug: cabozantinib

drug: cabozantinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Noel Jaclyn Del Toro

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