Encorafenib (BRAFTOVI®): A Comprehensive Pharmacological and Clinical Monograph

Section 1: Executive Summary & Drug Profile

Encorafenib, marketed under the brand name BRAFTOVI®, is an orally available, small-molecule kinase inhibitor that represents a significant advancement in the field of precision oncology.[1] It functions as a potent and selective inhibitor of the BRAF kinase, a key enzyme in the mitogen-activated protein kinase (MAPK) signaling pathway. The drug specifically targets cancers harboring activating mutations in the

BRAF gene, most notably the V600E and V600K substitutions, which act as oncogenic drivers in a variety of malignancies.[3]

The clinical utility of Encorafenib is defined by its use in rationally designed combination regimens. It is approved by regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), for the treatment of several advanced cancers. These indications include unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (in combination with the MEK inhibitor binimetinib), metastatic colorectal cancer (CRC) with a BRAF V600E mutation (in combination with the EGFR inhibitor cetuximab), and metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation (in combination with binimetinib).[2]

The rationale for these combination strategies is rooted in the complex biology of the MAPK pathway. Combining Encorafenib with a downstream MEK inhibitor mitigates the paradoxical pathway activation often seen with BRAF inhibitor monotherapy, a mechanism that can promote the growth of wild-type BRAF cells and lead to secondary malignancies.[7] In colorectal cancer, the addition of an EGFR inhibitor is necessary to overcome intrinsic resistance mechanisms mediated by feedback loops involving the EGFR receptor.