A Biomarker Study of Tivozanib in Subjects With Advanced Renal Cell Carcinoma

This is a Phase 2, open-label, single arm, multi-center, study of orally administered
tivozanib to approximately 100 subjects with advanced RCC. This study is designed to
evaluate biomarkers in blood and archived tissue samples, and their correlation with
clinical activity and/or treatment-related toxicity in subjects with advanced RCC, and
estimate the percentage of tivozanib-treated subjects who are progression-free at 6 months,
ORR, PFS, safety and tolerability, and PK. Subjects will be stratified by histology (clear
cell vs. non-clear cell) Enrollment of non-clear cell subjects will be limited to ≤ 30% of
the entire study population.

Study enrollment is anticipated to complete in approximately 9 months. Treatment duration is
estimated to last approximately 6 months from the subject‟s first dose of tivozanib with a
follow-up period of 30 days. After 6 months, treatment with tivozanib may continue by
participation in a rollover protocol (AV-951-09-901). Maximum duration of subject
participation in this Phase 2 study is approximately 8 months.