encorafenib + capmatinib

Encorafenib + capmatinib is an investigational combination of two targeted small molecule inhibitors: encorafenib, a BRAF inhibitor, and capmatinib, a selective MET inhibitor. Encorafenib inhibits the activity of mutant BRAF kinase (primarily V600E/K), interrupting the MAPK/ERK signaling pathway that drives growth in certain cancers. Capmatinib targets and inhibits the MET receptor tyrosine kinase, which is implicated in cancer cell proliferation, survival, and metastasis. This combination is being studied preclinically as a potential therapy for tumors harboring BRAF resistance mechanisms involving MET amplification or MET activity, especially in melanoma models that are resistant to MAPK pathway inhibitors. Preclinical models found the addition of capmatinib to encorafenib (sometimes with a MEK inhibitor) could overcome resistance and result in sustained tumor regression[6].