A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or 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. RAF265 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 RAF265 when administered orally to
subjects with locally advanced or metastatic melanoma; to determine the plasma
pharmacokinetics (PKs) of orally administered RAF265; and to evaluate potential
pharmacodynamic effects of RAF265 using tumor biopsies, peripheral blood samples, and tumor
imaging.