Compound DescriptionOral, selective B-Raf inhibitor
Areas of ResearchMelanoma and B-Raf mutant solid tumors
Proposed Mechanism of ActionRaf is a component of the mitogen-activated protein kinase (MAPK) signal-transduction pathway, which controls proliferation, differentiation, and apoptosis in mammalian cells through Ras, Raf, and extracellular-signal-regulated kinase (ERK) kinase (MEK).1 There are three isoforms of Raf: A-Raf, B-Raf, and C-Raf. Activating mutations of B-Raf have been identified in multiple cancers, most notably in melanomas but also in colorectal cancer, serous borderline ovarian cancer, and papillary thyroid carcinomas.1,2 The most common B-Raf mutation is V600E which accounts for 90% of all cancer causing B-Raf mutations.2,3
Encorafenib (LGX818) is small molecule selective Raf kinase inhibitor, with binding characteristics on B-RafV600E. The compound therefore suppresses the Raf/MEK/ERK pathway in tumor cells expressing B-RafV600E but does not evoke antiproliferative activity in wild-type B-Raf tumor cells.4
Key Preclinical DataIn preclinical studies Encorafenib has demonstrated activity in B-RafV600E human melanoma xenograft models as well as in mouse/rat xenograft models expressing B-RafV600E.4
Clinical StatusEncorafenib is being evaluated in melanoma, colorectal cancer, and other advanced solid tumors. In patients with melanoma harboring the B-Raf mutation, a Phase I study of oral Encorafenib and a Phase Ib/II study of is being evaluated in melanoma, colorectal cancer, and other advanced solid tumors. In patients with melanoma harboring the B-Raf mutation, a phase I study of oral Encorafenib and a phase Ib/II study of LGX818 in combination with encorafenib are underway.5,6 In colorectal cancer, a phase Ib/II multicenter, open-label dose escalation study of encorafenib (LGX818) and cetuximab, with or without BYL719, is ongoing in patients with BRAF mutant metastatic disease.7 In addition, a phase Ib/II dose escalation study is exploring encorafenib in combination with binimetinib (MEK162) in patients with BRAF V600-dependent advanced solid tumors.8
The information contained herein was last updated on April 12, 2013.
All Compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.
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