Tivozanib (VEGFR 123 TKI)
Tivozanib (FOTIVDA®) is an oral, once-daily, 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 modifications.1,2 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. Based on these positive topline results, and following consultation with the U.S. Food and Drug Administration (FDA) to discuss the results of an interim analysis of the study’s secondary endpoint of overall survival (OS), AVEO intends to submit a New Drug Application (NDA) for tivozanib in patients with relapsed/refractory RCC in the first quarter of 2020. AVEO is also evaluating tivozanib in combination with Bristol-Myers Squibb’s PD-1 inhibitor OPDIVO® (nivolumab) and AstraZeneca’s PD-L1 inhibitor IMFINZI® (durvalumab) in RCC and hepatocellular carcinoma, respectively.