Molecular Profile Detail

Profile Name BRAF V600E/K
Gene Variant Detail

BRAF V600E/K (gain of function)

Relevant Treatment Approaches BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). detail... detail... detail... 30219628
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). 30959471 detail...
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (COMBI-AD) that supported FDA approval, adjuvant treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved estimated 3-year relapse-free survival rate (58% vs 39%, HR=0.47, P<0.001) and 3-year overall survival rate (86% vs 77%, HR=0.57; 95% CI, 0.42 to 0.79, P=0.0006) compared to placebo in stage III melanoma patients harboring BRAF V600E or V600K mutations (PMID: 28891408; NCT01682083). detail... 28891408 detail...
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). detail... detail... 25399551
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011 detail... detail...
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292; NCT00687622). 22805292
BRAF V600E/K melanoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib + XL888 Phase I Actionable In a Phase I trial, combined Zelboraf (vemurafenib) and XL888 treatment in patients with unresectable, BRAF inhibitor naive, metastatic melanoma harboring BRAF V600E (n=20) or V600K (n=1) resulted in complete and partial responses in 15% (3/20) and 60% (12/20) of evaluable patients, respectively, a 9.2-month median progression free survival, and a 34.6-month overall survival (PMID: 29674508). 29674508
BRAF V600E/K lung non-small cell carcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Guideline Actionable The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first or second-line therapy in patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 30285222 detail...
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). detail... detail... 27480103
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
Clinical Trial Phase Therapies Title Recruitment Status
NCT01781026 Phase II Vemurafenib Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases Completed
NCT02721459 Phase I Cobimetinib + Vemurafenib + XL888 XL888 + Vemurafenib + Cobimetinib for Unresectable B Rapidly Accelerated Fibrosarcoma (BRAF) Mutated Stage III/IV Melanoma Active, not recruiting
NCT02027961 Phase Ib/II Dabrafenib + Durvalumab + Trametinib Durvalumab + Trametinib Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone Completed
NCT01767454 Phase I Dabrafenib + Ipilimumab + Trametinib Dabrafenib + Ipilimumab Study of Dabrafenib +/- Trametinib in Combination With Ipilimumab for V600E/K Mutation Positive Metastatic or Unresectable Melanoma Completed
NCT01989585 Phase Ib/II Dabrafenib + Navitoclax + Trametinib Dabrafenib + Trametinib Dabrafenib, Trametinib, and Navitoclax in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery Recruiting
NCT01682083 Phase III Dabrafenib + Trametinib A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. Active, not recruiting
NCT03455764 Phase Ib/II Dabrafenib + MCS110 + Trametinib A Phase I/II Study of MCS110 With BRAF/MEK Inhibition in Patients With Melanoma After Progression on BRAF/MEK Inhibition Recruiting
NCT01585415 Phase I Vandetanib Vemurafenib and White Blood Cell Therapy for Advanced Melanoma Terminated
NCT02200562 Phase Ib/II Dabrafenib + Ipilimumab Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma Terminated
NCT01978236 Phase II Dabrafenib + Trametinib Dabrafenib Dabrafenib/Trametinib, BRAF or BRAF AND MEK Pre-op With BRAF and MEK Post-op, Phase IIB, Melanoma With Brain Mets,Biomarkers and Metabolites Terminated
NCT02097225 Phase I Dabrafenib + Onalespib + Trametinib Hsp90 Inhibitor AT13387, Dabrafenib, and Trametinib in Treating Patients With Recurrent Melanoma That is Metastatic or Cannot be Removed by Surgery Active, not recruiting
NCT01495988 Phase II Bevacizumab Vemurafenib Trial of Vemurafenib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma Terminated
NCT03101254 Phase Ib/II Cobimetinib + LY3022855 + Vemurafenib LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma Recruiting
NCT01657591 Phase I Vemurafenib + XL888 Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma Active, not recruiting
NCT02427893 Phase III Cobimetinib Vemurafenib Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma Withdrawn
NCT02224781 Phase III Ipilimumab + Nivolumab Dabrafenib + Trametinib Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma Recruiting
NCT02818023 Phase I Pembrolizumab + Vemurafenib Dose-seeking and Efficacy Study of Pembrolizumab Plus Vemurafenib Advanced Melanoma Active, not recruiting
NCT01909453 Phase III Vemurafenib Encorafenib Binimetinib + Encorafenib Study Comparing Combination of LGX818 Plus MEK162 and LGX818 Monotherapy Versus Vemurafenib in BRAF Mutant Melanoma Active, not recruiting
NCT02196181 Phase II Dabrafenib + Trametinib Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery Active, not recruiting
NCT01512251 Phase Ib/II Buparlisib + Vemurafenib BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma Completed
NCT03551626 Phase III Dabrafenib + Trametinib Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes (COMBI-APlus) Recruiting
NCT01947023 Phase I Dabrafenib + Lapatinib Dabrafenib and Lapatinib Ditosylate in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery Active, not recruiting
NCT01940809 Phase II Dabrafenib Trametinib Ipilimumab Ipilimumab With or Without Dabrafenib, and/or Trametinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed By Surgery Active, not recruiting
NCT03272464 Phase I Dabrafenib + Itacitinib + Trametinib Phase I Study of INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors. Recruiting
NCT01682213 Phase II Dabrafenib Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation Completed