Tivozanib, a VEGF tyrosine kinase inhibitor, for the treatment of adult patients with advanced renal cell carcinoma
Tivozanib ( Fotivda ) is an oral, once-daily, vascular endothelial growth factor ( VEGF ) tyrosine kinase inhibitor ( TKI ) for the treatment of adult patients with advanced renal cell carcinoma ( RCC ).
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.
Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy.
Tivozanib is currently 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 renal cell carcinoma.
Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.
The TIVO-3 trial, together with the previously completed TIVO-1 trial of Tivozanib in the first line treatment of renal cell carcinoma, is designed to support a first and third line indication for Tivozanib in the U.S.
Tivozanib is also being evaluated in a phase 1/2 trial in combination with anti-PD-1 therapy, Nivolumab in renal cell carcinoma, known as the TiNivo trial.
Tivozanib’s distinct tolerability profile among VEGF TKIs makes it a potentially unique candidate for use with PD-1 inhibitors.
In August 2017, the European Commission ( EC ) approved Fotivda ( Tivozanib ) for the treatment of adult patients with renal cell carcinoma in the European Union plus Norway and Iceland.
Tivozanib is indicated for the first line treatment of adult patients with advanced RCC and for adult patients who are vascular endothelial growth factor receptor ( VEGFR ) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced renal cell carcinoma.
The vascular endothelial growth factor ( VEGF ) pathway plays a significant role in angiogenesis, which is critical in cancer.
Angiogenesis, the formation of new blood vessels, is essential for endothelial cell proliferation, migration and survival.
There are five known VEGF ligands ( A, B, C, D, PLGF ) and three VEGF receptors ( 1, 2 and 3 ). Each ligand exhibits distinct but overlapping binding profiles for the three VEGF receptors.
To optimally inhibit the VEGF pathway it may be critical to effectively block all three VEGF receptors as each plays an important role in cancer angiogenesis: VEGF receptor 1 is critical for the modulation of endothelial cell survival and vessel morphogenesis; VEGF receptor 2 is thought to be the predominant receptor for endothelial cell proliferation and migration; and, VEGF receptor 3 promotes endothelial sprouting and vascular network formation.
Preclinical studies have demonstrated Tivozanib is a potent, selective, long half-life inhibitor of all three VEGF receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities. ( Xagena )
Source: Aveo Oncology, 2017