Encorafenib

Encorafenib is a drug with the molecular formula: C22H27Cl1F1N7O4S1, is a member of the family of protein kinase inhibitors (MAP-kinase inhibitor) which inhibits the function of the protein BRAF (Braf). Encorafenib - is used in combination with binimetinib - to treat adults with non-resectable or metastatic melanoma with a BRAF V600 mutation and is approved for this indication.

Encorafenib is a highly selective, ATP-competitive, small molecule inhibitor of the RAF kinase that suppresses the RAF/MEK/ERK signaling pathway in tumor cells that express different mutations of the BRAF kinase (V600E, D and K). Encorafenib does not suppress the RAF/MEK/ERK signalling pathway in cells expressing the BRAF wild-type.

The combination of Encorafenib and the MEK inhibitor binimetinib leads to higher antitumour activity. It also prevents the development of resistance and improves tolerability to BRAF inhibitor monotherapy.

The recommended dose for Encorafenib is 450 mg/day p.o. in combination with binimetinib. Encorafenib is rapidly absorbed with a median Tmax of 1.5-2 hours. Encorafenib can be taken with or without food. It is excreted in equal parts by faeces and urine, with a terminal half-life of 6.32 hours.

Those with Encorafenib and Binimetinib in the standard dosage very frequently (>= 1/10) observed: anemia, peripheral neuropathy, dizziness, headache, visual disturbances, detachment of retinal pigment epithelium, bleeding, hypertension, abdominal pain, diarrhea, vomiting, nausea, constipation, hyperkeratosis, rash, dry skin, Pruritus, alopecia, arthralgia, muscle diseases / myalgia, back pain, pain in the extremities, pyrexia, peripheral edema, fatigue, increase creatine kinase in the blood, increase transaminases, increase gamma-glutamyl transferase.

The trade name of Encorafenib is Braftovi®

In June 2018, the US Food and Drug Administration (FDA) approved encorafenib in combination with binimetinib. The European Commission approved the compound in September 2018.

Patients must have a BRAF V600 mutation detected before starting treatment with the combination encorafenib/binimetinib. Only patients with tumors expressing a BRAF V600E and V600K mutation have been shown to be effective and safe with encorafenib. Encorafenib is not approved and indicated in patients with malignant melanoma of the BRAF wild-type.

1. Chapman PB et al(2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. BRIM-3 Study Group N Engl J Med 364:2507-2516.
2. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature 417: 949-54.
3. Schindler G et al (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta neuropath 121:397-405.