Tivozanib, is a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities. Tivozanib is currently being evaluated in an ongoing Phase 2 clinical study in patients with colorectal cancer as part of the BATON (Biomarker Assessment of Tivozanib in ONcology) clinical development program. The BATON program leverages AVEO’s proprietary Human Response Platform and is designed to help guide the clinical development of tivozanib.
AVEO’s partner Astellas is conducting BATON-CRC, an open-label, multicenter, randomized Phase 2 clinical trial, evaluating tivozanib in combination with modified FOLFOX6 (mFOLFOX6) compared to bevacizumab in combination with mFOLFOX6 as first-line therapy in patients with advanced metastatic colorectal cancer (CRC). In December 2013, data from a planned interim analysis of the Phase 2 study of tivozanib in patients with colorectal cancer indicate that the study is unlikely to meet the primary endpoint in the intent-to-treat patient population. Interim data are being evaluated, and AVEO and Astellas are in discussions regarding next steps.
VEGF in Solid Tumors
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.