The present invention provides various compositions and methods useful for the treatment of BRAF-mutant tumors, such as BRAFV600E-mutant tumors. In some embodiments such methods involve administration of three active agents—a RAF inhibitor, a MEK inhibitor, and an ERK inhibitor. The present invention also provides novel intermittent dosing regimens for these three active agents that maintain maximal anti-tumor efficacy while also minimizing toxicity.