Tivozanib (VEGFR 123 TKI)
Tivozanib (FOTIVDA®) is an oral, once-daily, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications1,2. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.
As part of a North American registration plan, tivozanib is being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced RCC. In November 2018, AVEO announced that the TIVO-3 trial met its primary endpoint of demonstrating a significant improvement in progression free survival (PFS) and that the study also demonstrated a significant improvement in the secondary endpoint of overall response rate (ORR). In May 2020, the Company announced the final hazard ratio for the study’s secondary endpoint of OS. On June 1, 2020, the U.S. Food and Drug Administration (FDA) accepted for filing the New Drug Application (NDA) for tivozanib as a treatment for relapsed or refractory RCC and assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 31, 2021.