Overview | Breast Cancer Clinical Trial
AVEO’s lead product candidate, 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 an oral, once-daily, investigational tyrosine kinase inhibitor that is currently being evaluated in ongoing Phase 2 clinical studies in patients with breast and 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). Patient enrollment in BATON-CRC is complete and results are expected in 2014.
In December 2012, AVEO and Astellas initiated patient enrollment in a randomized, double-blind, multicenter Phase 2 clinical trial, called BATON-BC, evaluating the efficacy of tivozanib in combination with paclitaxel compared to placebo in combination with paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer who have received no more than one systemic therapy for advanced or metastatic breast cancer.
Both BATON-CRC and BATON-BC incorporate pre-specified biomarker analyses, which may help identify patients more likely to be responsive or resistant to tivozanib therapy.
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.