Approximately 168 patients have received combination therapy with dabrafenib and trametinib at the proposed study doses (150 mg BID dabrafenib and 2 mg once daily trametinib) with a median follow-up time of 12.8 months. In the dose-escalation phase, PFS was longest for the group receiving the highest doses of dabrafenib and trametinib with an acceptable safety profile. Based on these data the combination of 150 mg BID of dabrafenib and 2.0 mg once daily of trametinib has been selected for this study. Mature randomized phase 2 trial (Part C in Figure 2 above) with a median follow up of 14.1 months showed a higher response rate (76% versus 54%, p=0.03) and a longer median PFS (9.4 months vs 5.8 months, hazard ratio (HR) 0.39, p<0.001) in MAPK inhibitor-naïve patients on the combination of the full dose of dabrafenib and trametinib compared with dabrafenib monotherapy.