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| Profile Name | BRAF V600E/K |
| Gene Variant Detail | |
| Relevant Treatment Approaches | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF V600E/K | skin melanoma | sensitive | RAF Inhibitor (Pan) | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| 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 | 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 | skin 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 cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). | 30959471 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 | 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 | 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 | 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 | 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 | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (S1320), intermittent dosing (3-week-off, 5-week-on) of Tafinlar (dabrafenib) and Mekinist (trametinib) did not improve median progression-free survival (5.5 v 9.0 months; HR=1.36, p=0.064, two-sided alpha=0.2) compared to continuous dosing in melanoma patients harboring BRAF V600E or V600K, and there were no significant differences in median overall survival, treatment response, or toxicity between the two treatment groups (PMID: 33020646; NCT02196181). | 33020646 |
| BRAF V600E/K | melanoma | predicted - sensitive | BRAF Inhibitor | BGB-283 | Case Reports/Case Series | Actionable | In a Phase I trial, Linfirafenib (BGB-283) treatment resulted in partial response in 15.1% (8/53) of solid tumor patients with BRAF mutations, including 5 of 23 patients with melanoma harboring BRAF V600E or V600K overall, and in the dose expansion phase 57.1% (4/7) patient with BRAF V600-mutant melanoma had a partial response (PMID: 32182156; NCT02610361). | 32182156 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT01682083 | Phase III | Dabrafenib + Trametinib | Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD). (COMBI-AD) | Active, not recruiting | USA | CAN | 23 |
| NCT02427893 | Phase III | Cobimetinib Vemurafenib | Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma | Withdrawn | USA | 0 |
| 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 | USA | CAN | 2 |
| NCT02097225 | Phase I | Dabrafenib + Onalespib + Trametinib | Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
| NCT03455764 | Phase Ib/II | Dabrafenib + MCS110 + Trametinib | MCS110 With BRAF/MEK Inhibition in Patients With Melanoma | Active, not recruiting | USA | 0 |
| 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) | Active, not recruiting | CAN | 22 |
| NCT03272464 | Phase I | Dabrafenib + Itacitinib + Trametinib | INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors. | Recruiting | USA | 0 |
| 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 | USA | 0 |
| 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 | USA | 1 |
| NCT01947023 | Phase I | Dabrafenib + Lapatinib | Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
| NCT02818023 | Phase I | Cobimetinib + Pembrolizumab + Vemurafenib | Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib Advanced Melanoma | Active, not recruiting | USA | 0 |
| NCT01512251 | Phase Ib/II | Buparlisib + Vemurafenib | BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma | Completed | USA | 0 |
| 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 | USA | 0 |
| NCT01657591 | Phase I | Vemurafenib + XL888 | Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma | Active, not recruiting | USA | 0 |
| NCT01989585 | Phase Ib/II | Dabrafenib + Navitoclax + Trametinib Dabrafenib + Trametinib | Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery | Recruiting | USA | 0 |
| NCT03101254 | Phase Ib/II | Cobimetinib + LY3022855 + Vemurafenib | LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma | Active, not recruiting | USA | 0 |
| 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 | USA | 0 |
| NCT01781026 | Phase II | Vemurafenib | Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases | Completed | USA | 0 |
| NCT01682213 | Phase II | Dabrafenib | Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation | Completed | USA | 0 |
| NCT01585415 | Phase I | Vandetanib | Vemurafenib and White Blood Cell Therapy for Advanced Melanoma | Terminated | USA | 0 |
| NCT04527549 | Phase II | Dabrafenib + Trametinib Dabrafenib + Hydroxychloroquine + Trametinib | Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma | Active, not recruiting | USA | 0 |
| NCT04655157 | Phase Ib/II | Encorafenib + Ipilimumab + Nivolumab Binimetinib + Encorafenib + Ipilimumab + Nivolumab | Safety and Efficacy in Participants With Metastatic BRAF-mutant Melanoma Treated With Encorafenib With and Without Binimetinib in Combination With Nivolumab and Low-dose Ipilimuma (QUAD01) | Recruiting | USA | 0 |
| NCT01495988 | Phase II | Bevacizumab Vemurafenib | Trial of Vemurafenib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma | Terminated | USA | 0 |
| NCT01909453 | Phase III | Vemurafenib Encorafenib Binimetinib + Encorafenib | Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (COLUMBUS) | Active, not recruiting | USA | CAN | 27 |
| NCT02200562 | Phase Ib/II | Dabrafenib + Ipilimumab | Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma | Terminated | USA | 0 |
| NCT01940809 | Phase II | Dabrafenib + Ipilimumab Ipilimumab + Nivolumab + Trametinib Dabrafenib + Ipilimumab + Trametinib Ipilimumab + Trametinib Dabrafenib + Ipilimumab + Nivolumab Ipilimumab Ipilimumab + Nivolumab Dabrafenib + Ipilimumab + Nivolumab + Trametinib | Ipilimumab With or Without Dabrafenib, Trametinib, and/or Nivolumab in Treating Patients With Melanoma That Is Metastatic or Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |