Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities.
In October 2012, AVEO announced detailed results from an exploratory, randomized Phase 2 study evaluating the combination of ficlatuzumab and gefitinib compared to gefitinib monotherapy in previously untreated Asian subjects with non-small cell lung cancer (NSCLC).
About the HGF/c-Met Pathway
HGF is the sole ligand that binds to and activates a receptor called c-Met. Activation of the HGF/c-Met pathway is believed to be important in normal processes in embryonic development and wound healing, but its dysregulation is believed to play a role in cancer development, metastasis and drug resistance. HGF/c-Met has also been shown to be one of the most potent drivers of tumor growth in AVEO’s Human Response Platform™.
HGF/c-Met over-expression is observed in many solid tumors including breast, colorectal, gastric, head and neck, lung and prostate, as well as hematologic malignancies. Additionally, c-Met and EGFR are frequently co-amplified and co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can render resistance to EGFR-targeted therapies, and vice-versa.
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.
3. Christensen JG, et al. Cancer Letters: 225:1-26.
4. Engelman JA, et al. Science. 316:1039-43.
5. Turke AB, et al. Cancer Cell. 17:77-88.
6. Yano S, et al. Cancer Res. 68:9479-87.