A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced RCC

Inclusion Criteria:

- 18 years or older

- Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of
which includes a VEGFR TKI other than sorafenib or tivozanib.

- Histologically or cytologically confirmed RCC with a clear cell component (subjects
with pure papillary cell tumor or other non-clear cell histologies, including
collecting duct, medullary, chromophobe, and unclassified RCC are excluded).

- Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST)
criteria Version 1.1.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy ≥ 3 months.

Exclusion Criteria:

- Prior treatment with sorafenib or tivozanib.

- More than 3 prior regimens for metastatic RCC.

- Known central nervous system (CNS) metastases other than stable, treated brain
metastases. Subjects with previously treated brain metastasis will be allowed if the
brain metastasis has been stable by neuroimaging without steroid treatment for at
least 3 months following prior treatment (radiotherapy or surgery).

- Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or
coagulation disorders.

- Significant serum chemistry abnormalities

- Significant cardiovascular disease, including: Active clinically symptomatic left
ventricular failure,uncontrolled hypertension, myocardial infarction, severe angina,
or unstable angina within 6 months prior to administration of first dose of study
drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring
anti-arrhythmic medications.

- Inadequate recovery from any prior surgical procedure or major surgical procedure
within 4 weeks prior to administration of first dose of study drug.

- Currently active second primary malignancy.