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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose Escalation: MTD/Recommended Dose

Primary Outcome 1 - Timeframe: Up to 6 months

Primary Outcome 2 - Measure: Dose Expansion: ORR

Primary Outcome 2 - Timeframe: Up to 31 months

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
• Lower Esophageal Cancer

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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Overall Contact

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Phone: 1-888-EXELIXIS (888-393-5494), 650-837-7400

Email: druginfo@exelixis.com

LOCATION