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| Gene | BRAF |
| Variant | V600E |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | BRAF V600E (previously reported as V599E) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600E confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity, downstream signaling, and the ability to transform cells in culture (PMID: 15035987, PMID: 29533785, PMID: 18697864). |
| Associated Drug Resistance | |
| Category Variants Paths |
BRAF mutant BRAF act mut BRAF V600E/K BRAF V600E BRAF mutant BRAF V600X BRAF V600E/K BRAF V600E |
| Transcript | NM_004333.6 |
| gDNA | chr7:g.140753336A>T |
| cDNA | c.1799T>A |
| Protein | p.V600E |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_004333.5 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_004333.6 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_001354609.1 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_004333 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| XM_005250045 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_001378474.1 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_001378468.1 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| NM_001354609.2 | chr7:g.140753336A>T | c.1799T>A | p.V600E | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E/K | skin melanoma | sensitive | 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 | 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 | sensitive | 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 | 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 | 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 | 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 | 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 | skin melanoma | sensitive | 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 | predicted - sensitive | 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 | 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 | 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 | predicted - sensitive | Lifirafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Lifirafenib (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 |
| BRAF act mut | melanoma | no benefit | Sorafenib | Phase II | Actionable | In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). | 22394203 16880785 |
| BRAF act mut | melanoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study | Actionable | In a systematic review, an analysis of several clinical trials demonstrated Opdivo (nivolumab) plus Yervoy (ipilimumab) resulted in improved overall survival (OS) compared to BRAF plus MEK inhibitor in BRAF-mutant advanced melanoma patients when considering the entire study period, and analysis of the period beginning 12 months after treatment initiation demonstrated significantly greater OS and progression-free survival (PMID: 33556898; NCT01844505, NCT01584648, NCT01597908, NCT01909453, NCT01689519). | 33556898 |
| BRAF act mut | colorectal cancer | predicted - sensitive | VX-11e + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). | 27974663 |
| BRAF act mut | colorectal cancer | sensitive | BCA101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BCA101 resulted in a tumor growth inhibition of 31% compared to 8% with Erbitux (cetuximab) in a BRAF-mutant colorectal cancer cell line and human peripheral blood mononuclear cells coimplantation xenograft model (PMID: 37074042). | 37074042 |
| BRAF act mut | colorectal cancer | predicted - sensitive | CC-91516 | Preclinical - Biochemical | Actionable | In a preclinical study, CC-91516 inhibited Mapk signaling in BRAF-mutant colorectal cancer cells (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). | detail... |
| BRAF act mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 |
| BRAF act mut | Advanced Solid Tumor | predicted - sensitive | CC-91516 | Preclinical - Patient cell culture | Actionable | In a preclinical study, CC-91516 treatment induced apoptosis and inhibited viability of cancer cells harboring BRAF activating mutations, and inhibited ex vivo colony formation from patient-derived xenograft (PDX) models in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). | detail... |
| BRAF act mut | melanoma | sensitive | Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). | 22084396 |
| BRAF act mut | lung non-small cell carcinoma | sensitive | RAF709 | Preclinical - Pdx | Actionable | In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). | 29343524 |
| BRAF act mut | Advanced Solid Tumor | sensitive | Binimetinib + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). | detail... |
| BRAF act mut | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). | 24422853 |
| BRAF act mut | colorectal cancer | no benefit | Venetoclax + VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 |
| BRAF mutant | colorectal cancer | no benefit | Regorafenib | Phase II | Actionable | In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). | 30120161 |
| BRAF mutant | melanoma | sensitive | Tubastatin A | Preclinical | Actionable | In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). | 25957812 |
| BRAF mutant | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study | Actionable | In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). | 31367539 |
| BRAF mutant | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF non-V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). | 30268448 |
| BRAF mutant | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | colorectal cancer | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | melanoma | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). | 24422853 |
| BRAF mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | colorectal cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | Advanced Solid Tumor | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF mutant | melanoma | sensitive | S63845 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). | 27760111 |
| BRAF mutant | melanoma | sensitive | Selumetinib | Case Reports/Case Series | Actionable | In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). | 22048237 |
| BRAF mutant | melanoma | sensitive | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 |
| BRAF mutant | Advanced Solid Tumor | decreased response | XL147 | Preclinical | Actionable | In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). | 25637314 |
| BRAF mutant | Advanced Solid Tumor | sensitive | Dabrafenib | Phase I | Actionable | In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). | 22608338 |
| BRAF mutant | colon cancer | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). | 26140595 |
| BRAF mutant | melanoma | sensitive | Vemurafenib + Voruciclib | Phase I | Actionable | In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). | detail... |
| BRAF mutant | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). | 28775144 |
| BRAF mutant | thyroid cancer | predicted - sensitive | Selumetinib | Phase I | Actionable | In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027). | 23406027 |
| BRAF mutant | melanoma | sensitive | Buparlisib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 |
| BRAF mutant | melanoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... |
| BRAF mutant | melanoma | sensitive | Encorafenib | Phase I | Actionable | In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). | 28611198 |
| BRAF mutant | colorectal cancer | sensitive | Tovorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ojemda (tovorafenib) demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). | 28611205 |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). | 28947956 |
| BRAF mutant | melanoma | predicted - sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Ulixertinib (BVD-523) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021; NCT01781429). | 29247021 |
| BRAF mutant | melanoma | sensitive | E6201 + LY294002 | Preclinical | Actionable | In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). | 23039341 |
| BRAF mutant | melanoma | sensitive | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 |
| BRAF mutant | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). | 22460902 |
| BRAF mutant | colorectal cancer | predicted - sensitive | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). | 28152546 |
| BRAF mutant | melanoma | sensitive | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). | 27488531 |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Case Reports/Case Series | Actionable | In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). | detail... |
| BRAF mutant | thyroid cancer | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... |
| BRAF mutant | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). | 23039341 |
| BRAF mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... |
| BRAF mutant | melanoma | sensitive | Tovorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ojemda (tovorafenib) demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... |
| BRAF mutant | melanoma | sensitive | Tovorafenib | Phase I | Actionable | In a Phase I trial, Ojemda (tovorafenib) treatment resulted in stable disease in 23% (5/22) of patients with advanced solid tumors in the dose escalation phase, an objective response rate of 15% (10/68) in the dose expansion phase with responses in 50% (8/16) of patients with RAF and MEK inhibitor-naive BRAF-mutant melanoma, an overall median duration of response of 6.0 months, and a median progression-free survival of 1.9 months (PMID: 37219686; NCT01425008). | 37219686 |
| BRAF mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in a patients with BRAF-mutant melanoma in a dose escalation study, and partial response in 33% (2/6) of BRAF-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... |
| BRAF mutant | colorectal cancer | decreased response | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). | 26351322 |
| BRAF mutant | lymphoma | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF mutant | colorectal cancer | predicted - sensitive | LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). | 28611205 |
| BRAF mutant | melanoma | predicted - sensitive | UNC2025 + Vemurafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852). | 30482852 |
| BRAF mutant | colorectal cancer | predicted - sensitive | Dabrafenib + Panitumumab + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). | 27770002 |
| BRAF mutant | Advanced Solid Tumor | no benefit | LY3009120 | Case Reports/Case Series | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116). | 31645440 |
| BRAF mutant | colon cancer | predicted - sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). | 27655129 |
| BRAF mutant | colorectal cancer | predicted - sensitive | SY-5609 | Preclinical - Pdx | Actionable | In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). | detail... |
| BRAF mutant | splenic marginal zone lymphoma | not applicable | N/A | Guideline | Diagnostic | BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org). | detail... |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | cervix carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | pancreatic adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | melanoma | predicted - sensitive | BI-847325 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). | 25873592 |
| BRAF mutant | pancreatic cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... |
| BRAF mutant | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... |
| BRAF mutant | melanoma | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). | 27307593 |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | Binimetinib + Encorafenib | Phase II | Actionable | In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in advanced solid tumor patients harboring BRAF non-V600E mutations including class 1 (n=1), class 2 (n=4), and class 3 (n=5), with an objective response rate of 22% (2/9) and a partial response in a patient with ampullary cancer harboring BRAF D594G and an unconfirmed PR in a melanoma patient harboring BRAF G469S (Annals of Oncology 32 (2021): S596; NCT03839342). | detail... |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). | 26140595 |
| BRAF mutant | colorectal cancer | sensitive | AZ628 + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). | 26351322 |
| BRAF mutant | melanoma | sensitive | PET-16 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). | 26984758 |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | Tovorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Ojemda (tovorafenib) inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). | detail... |
| BRAF mutant | colorectal cancer | sensitive | Belvarafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... |
| BRAF mutant | Advanced Solid Tumor | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). | 29343524 |
| BRAF V600X | skin melanoma | sensitive | Binimetinib + Encorafenib | Guideline | Actionable | Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | Binimetinib + Encorafenib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Mektovi (binimetinib) plus Braftovi (encorafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | melanoma | sensitive | Buparlisib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | skin melanoma | sensitive | Atezolizumab + Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) plus Cotellic (cobimetinib) in combination with an immune checkpoint inhibitor, such as Tecentriq (atezolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). | detail... |
| BRAF V600X | melanoma | predicted - sensitive | Dabrafenib + Spartalizumab + Trametinib | Phase III | Actionable | In a Phase III trial (COMBI-i), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Spartalizumab (PDR001) resulted in an objective response rate of 78% (28/36, 16 complete, 12 partial), disease control rate of 94% (34/36), and median progression-free survival of 23 months in patients with BRAF V600-mutant metastatic melanoma, including 29 patients (81%) harboring BRAF V600E and 4 patients (11%) harboring BRAF V600K (PMID: 33020648; NCT02967692). | 33020648 |
| BRAF V600X | skin melanoma | sensitive | Dabrafenib + Pembrolizumab + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) plus Mekinist (trametinib) in combination with an immune checkpoint inhibitor, such as Keytruda (pembrolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). | detail... |
| BRAF V600X | melanoma | sensitive | Selumetinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Selumetinib (AZD6244) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | melanoma | sensitive | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | melanoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, melanoma patients harboring BRAF V600 mutations (V600E/K/R/D or V600_K601delinsE) treated with the combination of Yervoy (ipilimumab) and Opdivo (nivolumab) demonstrated significantly improved median progression-free survival (10.1 vs 5.2 months; P=0.0057) and median overall survival (not reached vs 16.9 months; P<0.0001) compared to patients without BRAF V600 mutations (PMID: 36130145). | 36130145 |
| BRAF V600X | melanoma | sensitive | Atezolizumab + Cobimetinib + Vemurafenib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 71.8% (28/39), with a complete response in 20.5% (8/39), a median progression-free survival of 12.9 months, a median overall survival not yet reached, and median duration of confirmed response of 17.4 months (PMID: 31171876; NCT01656642). | detail... 31171876 |
| BRAF V600X | melanoma | sensitive | Atezolizumab + Cobimetinib + Vemurafenib | FDA approved | Actionable | In a Phase III trial (IMspire150) that supported FDA approval, addition of Tecentriq (atezolizumab) to Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy significantly improved progression-free survival (15.1 vs 10.6 months, HR=0.78, p=0.025) compared to control in patients with advanced or metastatic melanoma harboring BRAF V600 mutations (PMID: 32534646; NCT02908672). | 32534646 detail... |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Dabrafenib | Phase I | Actionable | In a Phase I trial (BRF116013), Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in a median duration of treatment of 75.6 week in pediatric patients with BRAF V600-mutant advanced solid tumors, including low-grade (n=15) and high-grade (n=8) gliomas, Langerhans cell histiocytosis (n=2), neuroblastoma (n=1), and papillary thyroid cancer (n=1) (PMID: 31506385; NCT01677741). | 31506385 |
| BRAF V600X | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Phase II | Actionable | In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer (PMID: 26287849; NCT01524978). | 26287849 |
| BRAF V600X | melanoma | predicted - sensitive | ABM-1310 + Cobimetinib | Case Reports/Case Series | Actionable | In a Phase I trial, the combination of ABM-1310 and Cotellic (cobimetinib) was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 1 partial response in a patient with melanoma and 1 stable disease among 3 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628). | detail... |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Tunlametinib + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 60.6% (20/33), a median duration of response of 11.3 months, and a median progression free survival of 11.7 months in patients with advanced non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). | detail... |
| BRAF V600X | skin melanoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF V600X | melanoma | sensitive | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in a partial response in 20% (8/41) of melanoma patients harboring BRAF V600 mutations, including V600E (33/41), V600K (5/41), and V600R (1/41) (PMID: 23414587; NCT01320085). | 23414587 |
| BRAF V600X | low grade glioma | predicted - sensitive | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment demonstrated a manageable safety profile in pediatric patients with BRAF V600-mutant low-grade glioma, and resulted in an objective response rate of 25% (9/36, all partial responses), a clinical benefit rate of 88.9% (32/36), a median duration of response of 33.6 months, and a median progression-free survival of 36.9 months (PMID: 36375115; NCT02124772). | 36375115 |
| BRAF V600X | melanoma | sensitive | Buparlisib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | melanoma | sensitive | Cobimetinib + Vemurafenib | Phase III | Actionable | In a Phase III trial, combination treatment with Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months compared to 7.2 months with Zelboraf (vemurafenib) alone among patients with BRAF V600-mutated metastatic melanoma (PMID: 27480103; NCT01689519). | 27480103 |
| BRAF V600X | brain cancer | predicted - sensitive | ABM-1310 | Phase I | Actionable | In a Phase I trial, ABM-1310 treatment was well tolerated and resulted in preliminary antitumor activity with 3 partial responses and 8 stable disease among 13 patients with brain tumors harboring BRAF V600 mutations, including a partial response in a patient with glioblastoma and 2 partial responses in patients with pleomorphic xanthoastrocytoma (Ann Oncol (2024) 35 (suppl_2): S411; NCT05892653). | detail... |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 42% (8/19, 8 partial responses) in patients with non-small cell lung cancer harboring BRAF V600 mutations, with a median progression-free survival of 7.3 months (PMID: 26287849; NCT01524978}. | 26287849 |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations (PMID: 31959346; NCT02304809). | 31959346 |
| BRAF V600X | lung non-small cell carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation, or as subsequent therapy in patients harboring BRAF V600 mutations that have not received prior BRAF/MEK inhibitor therapy (PMID: 30285222; ESMO.org). | detail... 30285222 |
| BRAF V600X | thyroid cancer | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 29% (2/7), with 1 complete response and 1 partial response, in patients with anaplastic thyroid cancer patients with BRAF V600 mutations (PMID: 26287849; NCT01524978). | 26287849 |
| BRAF V600X | colorectal cancer | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Zelboraf (vemurafenib) in colorectal cancer patients with BRAF V600 mutations did not result in clinical benefit, with no patients achieving response, and 50% (5/10) demonstrating progressive disease (PMID: 26287849; NCT01524978). | 26287849 |
| BRAF V600X | melanoma | sensitive | Buparlisib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Koselugo (selumetinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | cholangiocarcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in partial response in 12% (1/8) and stable disease in 50% (4/8) of cholangiocarcinoma patients with BRAF V600 mutations (PMID: 26287849; NCT01524978). | 26287849 |
| BRAF V600X | melanoma | predicted - sensitive | Binimetinib + Encorafenib + Pembrolizumab | Phase I | Actionable | In a Phase I trial (IMMU-Target), Mektovi (binimetinib), Braftovi (encorafenib), and Keytruda (pembrolizumab) demonstrated safety and preliminary efficacy in treatment naive patients with advanced melanoma harboring BRAF V600 mutations, resulting in an overall response rate of 64% (9/14), with a 12-month progression-free survival rate of 37.5% (n=8) and 60% (n=6) at the two tested dose levels, respectively (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9532; NCT02902042). | detail... |
| BRAF V600X | melanoma | sensitive | MK2206 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | ganglioglioma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Tafinlar (dabrafenib) treatment resulted in a partial response in a pediatric patient with BRAF V600-mutant ganglioglioma (PMID: 31811016; NCT01677741). | 31811016 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Cobimetinib + Vemurafenib | Phase II | Actionable | In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an objective response rate (ORR) of 50% (18/36), median progression-free survival of 7.9 months, and overall survival of 15.9 months in patients with advanced solid tumors harboring a BRAF V600 mutation and an ORR of 42% (10/24) in treatment-naive patients with non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2024) 35 (Suppl_2): S498). | detail... |
| BRAF V600X | melanoma | predicted - sensitive | Dabrafenib + Nivolumab + Trametinib | Phase II | Actionable | In a Phase II trial, combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Opdivo (nivolumab) resulted in an objective response rate (ORR) of 92% (24/27, 3 CR, 21 PR) in patients with MEK inhibitor-naive, BRAF V600-mutated melanoma, with a median progression-free survival of 8.5 mos, ORR was 88% (14/16) and 100% (10/10) in PD1 refractory or naive patients, 57% (4/7) of patients with brain metastasis achieved intracranial response (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9520; NCT02910700). | detail... |
| BRAF V600X | melanoma | predicted - sensitive | Dabrafenib + Hydroxychloroquine + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial (BAMM), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Plaquenil (hydroxychloroquine sulfate) resulted in a 1-year progression-free survival (PFS) rate of 48.2%, a median PFS of 11.2 mo, a response rate (RR) of 85% (29/34, 14 complete, 15 partial responses), and median overall survival (OS) of 26.5 mo in patients with advanced BRAF V600-mutant melanoma, RR, mPFS, and OS were 88%, 7.3, and 22 mo in patients with elevated LDH (n=16) (PMID: 35022320; NCT02257424). | 35022320 |
| BRAF V600X | colorectal cancer | predicted - sensitive | Tunlametinib + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 25.0% (6/24), a median duration of response of 5.5 months, and a median progression free survival of 6.2 months in patients with advanced colorectal cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). | detail... |
| BRAF V600X | skin melanoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as neoadjuvant or adjuvant therapy for stage III disease and as second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Tafinlar (dabrafenib) plus Mekinist (trametinib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | low grade glioma | predicted - sensitive | Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, Mekinist (trametinib) treatment demonstrated a manageable safety profile in pediatric patients with BRAF V600-mutant low grade glioma, and resulted in an objective response rate of 15.4% (2/13, all partial responses), a clinical benefit rate of 61.5% (8/13), a median progression-free survival of 16.4 months, and median duration of response not reached (PMID: 36375115; NCT02124772). | 36375115 |
| BRAF V600X | melanoma | sensitive | Atezolizumab + Vemurafenib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab) and Zelboraf (vemurafenib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 76.5% (13/17), with a complete response in 17.6% (3/17), a median progression-free survival of 10.9 months, a median overall survival of 46.2 months, and median duration of confirmed response of 10.6 months (PMID: 31171876; NCT01656642). | 31171876 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | ABM-1310 | Phase I | Actionable | In a Phase I trial, ABM-1310 treatment was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 2 partial responses (1 pleomorphic xanthroastrocytoma, 1 glioblastoma) and 8 stable diseases among 16 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628). | detail... |
| BRAF V600X | skin melanoma | sensitive | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | Cobimetinib + Vemurafenib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Cotellic (cobimetinib) plus Zelboraf (vemurafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | skin melanoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... |
| BRAF V600X | melanoma | sensitive | MK2206 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of MK2206 and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, combination treatment with Belvarafenib (HM95573) and Cotellic (cobimetinib) was well-tolerated and demonstrated safety, and led to a confirmed partial response in 33.3% (3/9) solid tumor patients harboring BRAF V600 mutations (Annals of Oncology 32 (2021): S595; NCT03284502). | detail... |
| BRAF V600X | low grade glioma | predicted - sensitive | Dabrafenib | Phase Ib/II | Actionable | In a Phase I/II trial, Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in an objective response rate of 44% (14/32, 1 complete response, 13 partial response) and a disease control rate of 78% (25/32), with a median duration of response of 26 months in pediatric patients with BRAF V600-mutant low-grade gliomas (PMID: 31811016; NCT01677741). | 31811016 |
| BRAF V600X | melanoma | sensitive | Dabrafenib + KRT-232 + Trametinib | Phase I | Actionable | In a Phase I trial, the combination therapy of KRT-232 (AMG 232), Mekinist (trametinib), and Tafinlar (dabrafenib) in 6 patients with metastatic cutaneous melanoma harboring a BRAF V600 mutation resulted in 4 patients with a partial response and 2 patients with stable disease, and of the 6 patients, all experienced tumor reduction (J Clin Oncol 35, 2017 (suppl; abstr 2575)). | detail... |
| BRAF V600X | melanoma | sensitive | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II clinical trial, patients with BRAF V600 mutant melanoma (n=78) treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) had a median overall survival of greater than 2 years (PMID: 26811525). | 26811525 |
| BRAF V600X | childhood low-grade glioma | sensitive | Tovorafenib | FDA approved | Actionable | In a Phase II trial (FIREFLY-1) that supported FDA approval, Ojemda (tovorafenib) was well tolerated and resulted in an overall response rate (ORR) per RAPNO criteria of 51% (39/76, 28 partial and 11 minor responses), clinical benefit rate (CBR) of 82% (62/76), and median duration of response of 13.8 mo in pediatric patients with low-grade glioma harboring BRAF fusions, rearrangements, or BRAF V600 mutations, with an ORR of 50% (6/12) in patients harboring BRAF V600E (PMID: 37978284; NCT04775485). | detail... 37978284 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | PLX8394 | Phase Ib/II | Actionable | In a Phase I/II trial, PLX8394 treatment resulted in a partial response in 39% (9/23) of patients with MAPK inhibitor-naive advanced solid tumors (excluding colorectal cancer) harboring BRAF V600X with a median duration of response of 32 months, and resulted in a partial response in 18% (3/17) and stable disease in 29% of patients previously treated with a MAPK inhibitor (J Clin Oncol 41, 2023 (suppl 16; abstr 3006); NCT02428712). | detail... |
| BRAF V600X | melanoma | sensitive | ASN003 | Preclinical - Pdx | Actionable | In a preclinical study, melanoma patient derived xenograft (PDX) model harboring a BRAF V600 mutation demonstrated antitumor activity when treated with ASN003 (J Clin Oncol 35, 2017 (suppl; abstr e14102)). | detail... |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Cobimetinib + Vemurafenib | Phase II | Actionable | In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an objective response rate (ORR) of 50% (18/36), median progression-free survival of 7.9 months, and overall survival of 15.9 months in patients with advanced solid tumors harboring a BRAF V600 mutation and an ORR of 42% (10/24) in treatment-naive patients with non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2024) 35 (Suppl_2): S498). | detail... |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Lifirafenib | Phase I | Actionable | In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 5 patients with BRAF V600E/K-mutant melanoma, 2 patients with BRAF V600E-mutant thyroid cancer, and 1 patient with BRAF V600E-mutant low-grade serous ovarian carcinoma, complete response in 1.9% (1/53), in a patient with melanoma, and stable disease in 50.9% (27/53) (PMID: 32182156; NCT02610361). | 32182156 |