The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of CHIR-265 in patients with locally advanced and metastatic melanoma.
The Ras/Raf/MEK/ERK pathway plays a prominent role in controlling several key cellular functions including growth, proliferation and survival. B-Raf is a member of the Ras/Raf/MEK/ERK pathway and is frequently mutated in melanoma resulting in activation of the MAPK pathway. CHIR-265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.
The primary objectives of this study are to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and the safety profile of CHIR-265 when administered orally to subjects with locally advanced or metastatic melanoma; to determine the plasma pharmacokinetics (PK) of orally administered CHIR-265; and to evaluate potential pharmacodynamic effects of CHIR-265 using tumor biopsies, peripheral blood samples, and tumor imaging.