New Amgen agents have potential for treating colon cancer

SAN DIEGO-Presentations at AACR 2008 highlighted two new agents under development by Amgen with potential for use in treating colorectal cancer.

AMG 386 is a recombinant Fc-peptide fusion protein designed to bind angiopoietins 1 and 2, thereby inhibiting Tie2-dependent stimulation of endothelial cells. Angiopoietins, together with VEGFs, are key cytokines that regular neovascularization. Preclinical studies of human colon tumor cells suggested a significantly greater reduction in tumor growth when AMG 386 was combined with a VEGF inhibitor-bevacizumab (Avastin) or motesanib diphosphate (AMG 706)-at suboptimal doses, compared with either treatment alone.

AMG 655, which targets death receptor 5, when combined with irinotecan (Camptosar) or 5-FU enhanced apoptosis relative to either agent alone in both in vitro and in vivo colon cancer cell models. AMG 655 is currently in a phase Ib/II trial in colorectal cancer.