AMG 479 is a fully human lgG1 monoclonal antibody against the type I insulin-like growth factor receptor (IGF-1R) under development by Amgen. It is believed to exert anti-tumor activity by blocking ligand binding and inducing receptor internalization and degradation without cross-reacting with the insulin receptor.
Like all monoclonal antibodies, it is administered intravenously.
NCI Drug Dictionary definition: ANG 479 is a recombinant, fully human monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Anti-IGF-1R fully human monoclonal antibody AMG-479 binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R is a tyrosine kinase and a member of the insulin receptor family. IGF-1R activation stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been highly implicated in tumorigenesis and metastasis.
Results from a Phase I trial were reported at the 2007 ASCO meeting (Abstract No: 3002)::
A phase I pharmacokinetic and pharmacodynamic study of AMG 479, a fully human monoclonal antibody against insulin-like growth factor type 1 receptor (IGF-1R), in advanced solid tumors.
AMG 479 is in numerous current trials (Phases I-II or II) directed against various cancers. The one most pertinent to GIST is shown below.
AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors
This trial combines inhibitors of IGF-1R and TRAIL.