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

Prior treatment

• 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.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.

Other illness

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

Other

• Pregnant or lactating females.

• 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.