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ENCORAFENIB (LGX818)
Phase 3, Phase 2, N/A, Phase 1/Phase 2
Selective B-Raf inhibitor
Hemat
LGX818 is an oral and selective B-Raf inhibitor. Areas of Research: Melanoma and B-Raf mutant solid tumors.

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

MOA data is based on in vitro/in vivo data. Clinical benefit is unknown.
Encorafenib (LGX818) is an investigational compound. Efficacy and safety have not been established.
There is no guarantee encorafenib (LGX818) will become commercially available.
References
  1. Wong KK. Recent developments in anti-cancer agents targeting the RAS/RAF/MEK/ERK pathway. Recent Pat Anticancer Drug Discov. 2009;4:28–35.
  2. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.
  3. Carnahan J, Beltran PJ, Babij C, et al. Selective and potent Raf inhibitors paradoxically stimulate normal cell proliferation and tumor growth. Mol Cancer Ther. 2010;9:2399–410.
  4. Novartis, data on file, 2014.
  5. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01436656. Updated January 14, 2014. Accessed January 16, 2014.
  6. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01777776. Updated January 15, 2014. Accessed January 16, 2014.
  7. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01719380. Updated October 24, 2013. Accessed January 14, 2014.
  8. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01543698. Updated November 18, 2013. Accessed January 14, 2014.
  9. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01820364. Updated October 29, 2013. Accessed January 14, 2014.
  10. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01894672. Updated January 9, 2014. Accessed January 14, 2014.
  11. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01909453. Updated September 26, 2013. Accessed January 14, 2014.

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.

The search results, details, and descriptions of clinical trials viewed in this app are supplied by ClinicalTrials.gov and EUtrialregistry.com. This information is maintained by a third party over whom Novartis Pharmaceuticals Corporation has no control. As such, Novartis Pharmaceuticals Corporation does not guarantee the accuracy, completeness, adequacy, or any other aspect of the information contained on this site.