Ficlatuzumab (AV-299)

Ficlatuzumab (AV-299), discovered by AVEO through its Human Response Platform™ (HRP), is a potent anti-HGF/c-MET antibody currently in Phase 2 development. In preclinical studies, AVEO showed that ficlatuzumab has additive activity when given in combination with approved anti-cancer agents such as erlotinib (Tarceva^®), cetuximab (Erbitux^®) and temozolomide (Temodar^®).

 

Clinical data from Phase 1 studies of ficlatuzumab indicate a favorable tolerability profile^1-2 and good combinability with EGFR inhibitors, erlotinib¹ and gefitinib² (Iressa^®), and no dose-limiting toxicities up to the highest dose tested (20 mg/kg)^1-2. In June 2011, AVEO announced that patient enrollment has been completed in its ongoing Phase 2 trial evaluating ficlatuzumab in combination with gefitinib as first-line therapy for patients with wild-type and mutant EGFR non-small cell lung cancer (NSCLC). Top-line data from the ficlatuzumab Phase 2 trial are expected in 2012. AVEO holds worldwide development and commercialization rights for ficlatuzumab.

 

 

About the HGF/c-MET Pathway

 

The HGF/c-MET pathway is believed to play an important role in regulating tumor growth, invasion and metastasis, making it an important, novel target in oncology. HGF/c-MET over-expression is observed in many tumors including bladder, lung, breast, gastric, ovarian, prostate, colorectal, head and neck, certain sarcomas and several other solid tumors as well as hematologic malignancies. The HGF/c-MET pathway has only one known ligand (HGF) that binds to one known receptor (c-MET) to initiate signaling. Ficlatuzumab is a potent anti-HGF/c-MET antibody with high affinity for the HGF ligand.

 

 

In addition, industry research suggests that increased HGF and/or c-MET receptor amplification may confer resistance to epidermal growth factor receptor (EGFR) inhibitors. Encouraging Phase 2 clinical data have been reported with other agents in development, a small molecule c-MET inhibitor and an antibody to c-MET, in combination with an EGFR tyrosine kinase inhibitor (TKI) in patients with advanced, refractory NSCLC. These data suggest the potential patient benefit from combination therapy of an EGFR TKI and an inhibitor of the HGF/c-MET pathway. There are currently no approved therapies that target the HGF/c-MET pathway.

 

 

1. Patnaik, A., et al. Poster presented at the 2010 ASCO Annual Meeting; June 4-8, 2010; Chicago, IL. Abstract 2525.
2. Tan, E., et al. Poster presented at the 2011 ASCO Annual Meeting; June 3-7, 2011; Chicago, IL. Abstract 7571.