The most common adverse events (AEs) attributed to either vemurafenib or GDC-0973 in the 70 patients treated to date were: non-acneiform rash (52.9%; 7.1% Grade 3 or 4), diarrhea (51.4%; 5.7%), photosensitivity/sunburn (31.4%; 0%), fatigue (30.0%; 1.4%), and nausea (28.6%; 1.4%). Selected AEs attributed to either vemurafenib or GDC-0973 were: creatinine phosphokinase elevation (20.0%; 4.3%), liver function test elevation (20.0%; 4.3%), arthralgia (12.9%; 1.4%), serous choreoretinopathy (4.3%; 0%), and cutaneous squamous cell carcinoma (1.4%; 1.4%).Temporary interruptions in vemurafenib, GDC-0973, or the combination of both agents were reported in 24.3%, 21.4%, and 8.6% of patients, respectively. One patient receiving the combination discontinued vemurafenib permanently because of QT interval prolongation. No patients receiving the combination of vemurafenib and GDC-0973 discontinued treatment due to an adverse event. All 24 BRAFi-naïve patients evaluable for tumor responses had a decrease in tumor size from baseline, however, further follow-up is required to determine the confirmed objective response rate. About GDC-0973 (XL518) GDC-0973 is a potent, highly selective inhibitor of MEK, a serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK pathway. This pathway mediates signaling downstream of growth factor receptors, and is prominently activated in a wide variety of human tumors. In preclinical studies, oral dosing of GDC-0973 resulted in potent and sustained inhibition of MEK in RAS or BRAF mutant tumor models. GDC-0973 is being developed by Genentech, a member of the Roche Group under a collaboration agreement with Exelixis. About Collaboration Exelixis discovered GDC-0973 (XL518) internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Exelixis was responsible for development of GDC-0973 through the end of Phase I, at which point Genentech exercised its option to further develop the compound.