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| Gene | BRAF |
| Variant | V600Q |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | BRAF V600Q (previously reported as V599Q) lies within the activation segment and the protein kinase domain of the Braf protein (PMID: 15035987). V600Q has been identified in the scientific literature (PMID: 28848703), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Mar 2020). |
| Associated Drug Resistance |
| Transcript | NM_004333 |
| gDNA | chr7:g.140753336_140753337delACinsTG |
| cDNA | c.1798_1799delGTinsCA |
| Protein | p.V600Q |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| XM_005250045 | chr7:g.140753336_140753337delACinsTG | c.1798_1799delGTinsCA | p.V600Q | RefSeq | GRCh38/hg38 |
| NM_004333 | chr7:g.140753336_140753337delACinsTG | c.1798_1799delGTinsCA | p.V600Q | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600X | colorectal cancer | sensitive | Cetuximab + Irinotecan + Vemurafenib | Phase Ib/II | Actionable | In a Phase Ib trial, the addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 mo vs. 2.0 mo), and disease control rate (67% vs. 22%), compared to Camptosar (irinotecan) plus Erbitux (cetuximab) without Zelboraf (vemurafenib), in patients with BRAF V600-mutant colorectal cancer (J Clin Oncol 35, 2017 (suppl 4S; abstract 520)). | detail... |
| BRAF V600X | malignant 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 | thyroid gland cancer | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical 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). | 26287849 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | BGB-283 | 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 |
| 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 | skin melanoma | sensitive | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| 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 | 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 | skin melanoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with cutaneous melanoma harboring a BRAF V600 activating mutation, as adjuvant treatment for patients with Stage III disease, or as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). | detail... |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Phase II | Actionable | In a Phase II clinical 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). | 26287849 |
| 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 | 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 | colorectal cancer | no benefit | Vemurafenib | Phase II | Actionable | In a Phase II clinical 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). | 26287849 |
| 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 | cholangiocarcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical 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). | 26287849 |
| 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 | 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 | 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 | colorectal cancer | sensitive | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in partial response or better in 12% (5/43), including 1 complete response, and stable disease in 51% (22/43) of patients with BRAF V600-mutant colorectal cancer (PMID: 26392102). | detail... 26392102 |
| 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 | 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 | lung non-small cell carcinoma | sensitive | 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 detail... 30285222 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | sensitive | MLN2480 | Phase I | Actionable | In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). | detail... |
| BRAF mutant | melanoma | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | 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 | 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 | 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 | 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 | 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 | 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 | 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 | sensitive | Alpelisib + Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). | detail... 28363909 |
| 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 | thyroid gland 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 | 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 | 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 | melanoma | predicted - sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) 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). | 29247021 |
| 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 | 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 | thyroid gland 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | colorectal cancer | sensitive | Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). | 28363909 |
| 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 | 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 | 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 | colorectal cancer | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | MLN2480 | Preclinical - Cell culture | Actionable | In a preclinical study, MLN2480 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 | 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 | Advanced Solid Tumor | sensitive | RAF709 | Phase I | 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 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 | 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 | 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 | 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 | 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 |
| Molecular Profile | Protein Effect | Treatment Approaches |
|---|---|---|
| BRAF V600Q | unknown | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) |