The present disclosure provides a combination therapy for treating cancer with BRAF mutations comprising administrating to a subject an effective amount of (a) an epidermal growth factor receptor (EGFR) inhibitor; (b) a mitogen-activated protein kinase (MEK) 1/2 inhibitor; and (c) a cyclin dependent kinase (CDK) 4/6 inhibitor. Also provided are compositions and kits related to the combination therapy.