Encorafenib in combination with binimetinib and cetuximab for BRAF V600E mutant metastatic colorectal cancer
Encorafenib in combination with binimetinib and cetuximab (triple therapy) is in clinical development for the treatment of patients with BRAF V600E mutant metastatic colorectal cancer (mCRC) whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. Colorectal (or bowel) cancer starts in the large bowel (colon) and the back passage (rectum) and is more common in people aged over 70 years. Its cause is unknown but various factors increase the risk of contracting it, including diet, smoking, and overweight or obesity. Around 10% of mCRC patients have the BRAF V600E mutation, and they have more than double the mortality risk of those without it.
Encorafenib in combination with binimetinib and cetuximab is one of the first regimens to target the BRAF V600E-mutation in colorectal cancer. When this mutation is present, it switches on another protein called MEK, which stimulates cell division and leads to uncontrolled cell growth. Encorafenib and binimetinib target different parts of an important signalling pathway in tumour cells with the mutation, and slows down their growth and communication. It is also one of the first combinations to simultaneously target the BRAF and MEK pathways, and encorafenib and binimetinib have the advantage of oral administration.