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

- 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, CRC, H&N, and DTC.

- Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of
single-agent cabozantinib in UC and NSCLC subjects

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, 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, 7,19 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.