Results from in vivo human tumor models in mice demonstrated significant inhibition of tumor growth in a broad range of cancer types. In c-Met driven gastric cancer and glioblastoma tumor models, MGCD265 decreased tumor volume by more than 95% compared to untreated tumors.
Furthermore, MGCD265 showed anti-tumor activity in breast, colorectal and non-small cell lung cancer tumor models that were not c-Met driven, with an average reduction in tumor volume of 76%. MGCD265 potently inhibited c-Met and VEGFR2 cellular phenotypes, including cell motility and angiogenesis. Biomarker analysis also revealed potent inhibition of in vivo c-Met signal transduction activity and inhibition of downstream Erk and Akt signaling pathways.
MethylGene expects to commence a dose-escalating, Phase I clinical trial (trial 102) for this compound in solid tumor cancers in April 2008, followed by a second Phase I trial in the second quarter of 2008.