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Therapy Name | Dabrafenib + Trametinib |
Synonyms | |
Therapy Description | |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Dabrafenib | Tafinlar | GSK2118436 | BRAF Inhibitor 25 | Tafinlar (dabrafenib) inhibits the activity of BRAF, including V600E, which results in the inhibition of tumor cell proliferation (PMID: 22735384). Tafinlar (dabrafenib) is FDA approved for BRAF V600E/K- positive unresectable or metastatic melanoma, and in combination with Mekinist (trametinib) for BRAF V600E/K-mutant melanoma, BRAF V600E-mutant non-small cell lung cancer, BRAF V600E-mutant anaplastic thyroid cancer, for adult and pediatric patients of 6 years or older with unresectable or metastatic solid tumors harboring BRAF V600E, and for pediatric patients of 1 year or older with low-grade glioma harboring BRAF V600E (FDA.gov). |
Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | Mekinist (trametinib) inhibits MEK 1 and 2, which potentially leads to reduced tumor cell proliferation (PMID: 27956260). Mekinist (trametinib) is FDA approved for melanoma patients harboring BRAF V600E or BRAF V600K mutations, and in combination with Tafinlar (dabrafenib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, BRAF V600E-mutant anaplastic thyroid cancer, for adult and pediatric patients of 6 years or older with unresectable or metastatic solid tumors harboring BRAF V600E, and for pediatric patients of 1 year or older with low-grade glioma harboring BRAF V600E (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF K601E | pancreatic endocrine carcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 31158244). | 31158244 |
BRAF R239Q BRAF L597S | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a patient-derived melanoma cell line harboring BRAF L597S, as well as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 100% (13/13) of subcutaneous tumors, and decreased growth of intracranial tumors in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
BRAF V600E MAP2K1 P124Q | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q in culture (PMID: 36442478). | 36442478 |
BRAF V600E NRAS A146T | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
BRAF V600E | stomach cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | Adenocarcinoma of Unknown Primary | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | high grade glioma | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an overall response rate of 56.1% (23/41; 12 complete, 11 partial responses), a clinical benefit rate of 65.9% (27/41), median duration of response of 22.2 months, median progression-free survival of 9.0 months, and median overall survival of 32.8 months in pediatric patients with relapsed or refractory high-grade glioma harboring BRAF V600E (PMID: 37643378; NCT02684058). | 37643378 |
BRAF V600E | high grade glioma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring BRAF V600E, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org). | detail... |
BRAF V600E | high grade glioma | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 33% (15/45, 3 complete responses, 12 partial responses) in patients with high-grade glioma harboring BRAF V600E, with a median duration of response of 36.9 months, a median progression-free survival of 3.8 months, and an overall survival of 17.6 months (PMID: 34838156; NCT02034110). | 34838156 |
BRAF V600E | high grade glioma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response in a pediatric patient with posterior fossa high grade glioma harboring BRAF V600E and deletion of CDKN2A (PMID: 39399174). | 39399174 |
BRAF V600E MAP2K1 F53Y | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53Y in culture (PMID: 36442478). | 36442478 |
BRAF V600E | anaplastic oligodendroglioma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). | detail... |
BRAF V600E MAP2K1 D67N | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N in culture (PMID: 36442478). | 36442478 |
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 V600E | biliary tract cancer | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) in combination with Mekinist (trametinib) demonstrated a manageable safety profile and resulted in an overall response rate of 51% (22/43, all partial responses) in patients with biliary tract cancer harboring BRAF V600E, with a median duration of response of 9 months, a median progression-free survival of 9 months, and a median overall survival of 14 months (PMID: 32818466; NCT02034110). | 32818466 |
BRAF V600E | biliary tract cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as second or later-line therapy for patients with biliary tract cancer harboring BRAF V600E (PMID: 36372281; ESMO.org). | 36372281 detail... |
BRAF V600E | biliary tract cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E (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 | 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 V600E MAP2K1 P105_A106del | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P105_A106del in culture (PMID: 36442478). | 36442478 |
BRAF T599dup | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in 12.3% tumor shrinkage in a patient with lung adenocarcinoma harboring BRAF T599dup along with KRAS Q61H, however, treatment was discontinued for adverse events (PMID: 38662982). | 38662982 |
BRAF T599dup | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring BRAF T599dup demonstrated a response to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), with regression of the left lower lobe bronchial tumor (PMID: 33704186). | 33704186 |
BRAF V600K NRAS Q61K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
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 V600E TP53 C176R | pancreatic adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic pancreatic adenocarcinoma harboring BRAF V600E and TP53 C176R was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) and achieved radiographic and biochemical responses with stabilization or reduction of lesions in the pancreas, lung, and liver, and remained on treatment despite progression of a single liver lesion after 8 months (PMID: 33250737). | 33250737 |
BRAF S363F BRAF K601E | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF V600E MAP2K1 C121S | melanoma | resistant | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 |
BRAF V600E | low grade glioma | sensitive | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial (Study X2101), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment demonstrated manageable toxicity and resulted in an objective response rate of 25% (9/36, 1 complete response, 8 partial responses) and stable disease in 67% (24/36) of pediatric patients with pretreated low-grade glioma harboring BRAF V600E (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02124772). | detail... |
BRAF V600E | low grade glioma | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 69% (9/13, 1 complete response, 6 partial responses, 2 minor responses) in patients with low-grade glioma harboring BRAF V600E, with median duration of response, median progression-free survival, and overall survival time unreached (PMID: 34838156; NCT02034110). | 34838156 |
BRAF V600E | low grade glioma | sensitive | Dabrafenib + Trametinib | FDA approved | Actionable | In a Phase II trial that supported FDA approval, Mekinist (trametinib) plus Tafinlar (dabrafenib) significantly improved overall response rate (47% vs 11%, risk ratio 4.31, p<0.001), clinical benefit rate (86% vs 46%), median progression-free survival (PFS, 20.1 vs 7.4 months, p<0.001, HR 0.31), and 12-month PFS rate (67% vs 26%) compared to standard chemotherapy in pediatric patients of 1 year and older with low-grade glioma harboring BRAF V600E (PMID: 37733309; NCT02684058). | detail... detail... 37733309 |
BRAF V600E | low grade glioma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | Advanced Solid Tumor | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in an objective response rate of 33.3% (11/33) in patients with advanced solid tumors other than melanoma, thyroid, colorectal, and lung cancer harboring BRAF V600E, with a median duration of response of 12 months, median progression-free survival of 9.4 months, and median overall survival not reached (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002; NCT02465060). | detail... |
BRAF V600E | Advanced Solid Tumor | sensitive | Dabrafenib + Trametinib | FDA approved | Actionable | In 3 Phase II trials (ROAR, NCI-MATCH, X2101) that supported FDA approval, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy demonstrated safety and efficacy in adult and pediatric (6 years or older) patients with advanced solid tumors harboring BRAF V600E (PMID: 34838156, PMID: 32818466, J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002, J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02034110, NCT02465060, NCT02124772). | 32818466 detail... detail... 34838156 detail... detail... |
BRAF G466A | collecting duct carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in decreased FDG avidity in the metastases in a patient with metastatic Bellini duct carcinoma harboring BRAF G466A, whose disease remained stable for 11 months (PMID: 33669326). | 33669326 |
BRAF V600E IDH1 R132C | lung squamous cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with a progression-free survival of 14.8 months, an overall survival of 34.6 months, and a duration of treatment of 14.9 months in a patient with squamous non-small cell lung cancer harboring BRAF V600E and IDH1 R132C (PMID: 39500140). | 39500140 |
BRAF V600E NRAS Q61K | lung adenocarcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). | 29631033 |
BRAF V600E | basal cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in stable disease after three months of treatment in a patient with basal cell carcinoma harboring BRAF V600E (PMID: 33537843) | 33537843 |
BRAF V600E | papillary thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a papillary thyroid carcinoma patient who progressed on Lenvima (lenvatinib) was found to harbor BRAF V600E and was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) on a clinical trial, resulting in partial response in the thyroid bed, cervical and intrathoracic lymph nodes, and pulmonary lesions, with a decrease in target lesion size of 67%, and the patient remained on treatment for 18 months before stopping due to progression (PMID: 31085763). | 31085763 |
BRAF V600E | papillary thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with papillary thyroid carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org). | detail... |
BRAF V600E | pancreatic endocrine carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response lasting at least 15 months in a patient with unresectable, metastatic pancreatic neuroendocrine carcinoma harboring BRAF V600E (PMID: 38814411). | 38814411 |
BRAF V600E | esophagus adenocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal adenocarcinoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | colon neuroendocrine neoplasm | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a clinical improvement and reduction of the primary tumor as well as the metastatic lesions in a cecal neuroendocrine carcinoma patient harboring BRAF V600E (PMID: 30036245). | 30036245 |
BRAF V600E | colon neuroendocrine neoplasm | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical study, second-line treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response in two patients with a neuroendocrine carcinoma of the colon harboring BRAF V600E, with progression-free survival of 6 months in one patient and 4 months in the second patient (PMID: 38716076). | 38716076 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 8 weeks of treatment in a patient with metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 36505826). | 36505826 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, third-line treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response lasting 18 months in a patient with KRAS wild-type, metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 38770091). | 38770091 |
BRAF V600E | pancreatic acinar cell adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with pancreatic acinar cell carcinoma harboring BRAF V600E who had previously progressed on chemotherapy led to a response at 8 weeks, and ongoing clinical and radiological response was still observed at 32 months of treatment (PMID: 33537843). | 33537843 |
BRAF V600E | pancreatic acinar cell adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in near complete remission allowing for debulking surgery and disease control for 12 months in a patient with metastatic pancreatic acinar cell carcinoma harboring BRAF V600E, along with germline PALB2 R414* (PMID: 32843432). | 32843432 |
BRAF G469A | lung non-small cell carcinoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a reduction of the liver tumor and stable disease in the brain lesion in a patient with non-small cell lung cancer harboring BRAF G469A (PMID: 32981611). | 32981611 |
BRAF G469A | lung non-small cell carcinoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased viability and enhanced ERK inhibition compared to either agent alone, in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 28947956). | 28947956 |
BRAF V600E | 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 | melanoma | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). | 28268064 |
BRAF V600E | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
BRAF V600E NRAS Q61K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
BRAF V600E NRAS Q61K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) moderately inhibited tumor growth in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). | 37729428 |
BRAF V600E | anaplastic pleomorphic xanthoastrocytoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in an ongoing partial response 8 months after initiation of treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, and a near complete response after 3 months of treatment in another patient with relapsed disease (PMID: 28984141). | 28984141 |
BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) led to a partial response after 1 month of treatment in a metastatic pancreatic ductal adenocarcinoma patient harboring BRAF V600E, followed by disease progression, which was detected 12 months later (PMID: 35382161). | 35382161 |
BRAF V600E | follicular thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with follicular thyroid carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org). | detail... |
BRAF V600E | anaplastic astrocytoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
BRAF G469R | large cell neuroendocrine carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a durable response in a patient with large cell neuroendocrine carcinoma of the lung harboring BRAF G469R, along with ERBB4 (HER4) A118S, STK11 L282fs, TP53 R248L and MYC amplification and led to a decrease in BRAF G469R in cell-free DNA (PMID: 35135105). | 35135105 |
BRAF V600K | 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... 25399551 detail... |
BRAF V600E | ovarian serous carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a complete response after 8 months of treatment in a patient with low-grade serous ovarian carcinoma harboring BRAF V600E (PMID: 33043759). | 33043759 |
BRAF V600E | ovarian serous carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a partial response lasting at least 2.5 years in one patient with low grade serous ovarian carcinoma harboring BRAF V600E, and resulted in a complete metabolic response after 4 months of treatment in a second patient (PMID: 35242981). | 35242981 |
BRAF V600E | breast metaplastic carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response in a patient with metaplastic breast cancer harboring BRAF V600E, however, progression occurred after 8 weeks (PMID: 32206360). | 32206360 |
BRAF G466V | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, first-line treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response after 3 months in a patient with metastatic lung adenocarcinoma harboring BRAF G466V (PMID: 38283732). | 38283732 |
BRAF V600E MAP2K1 P162S | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K1 P162S in culture (PMID: 24265154). | 24265154 |
BRAF V600E | epithelial predominant Wilms' tumor | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a complete radiographic response 4 months after treatment initiation that was maintained for at least 12 months in a pediatric patient with metastatic epithelial-predominant Wilms tumor harboring BRAF V600E (PMID: 32238401). | 32238401 |
BRAF V600E | glomus tumor | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in decreased tumor size lasting at least 9 months in an adolescent (18 years old) patient with malignant glomus tumor harboring BRAF V600E (PMID: 30556047). | 30556047 |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination therapy of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in improved clinical symptoms in a patient with epithelioid glioblastoma harboring BRAF V600E, and treatment of the patient's cells resulted in decreased cell viability, reduced phosphorylation of Mek and Erk, increased apoptotic activity compared to either agent alone, and cell cycle arrest in culture, and led to tumor growth suppression in the patient-derived xenograft (PDX) model (PMID: 31345255). | 31345255 |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, an epithelioid glioblastoma patient harboring BRAF V600E treated with Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy resulted in stable disease, and the patient continued to demonstrate stable disease at least 16 months after initiation of therapy (PMID: 29632053). | 29632053 |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a complete resolution of symptoms and radiographic partial response after the first treatment in a patient with glioblastoma harboring BRAF V600E whose disease progressed on PLX8394 treatment, and a complete response after 11 months of treatment, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904). | 32923904 |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response in 32% (10/31, 2 complete responses, 8 partial responses) and stable disease in 19% (6/31) of patients with glioblastoma harboring BRAF V600E (PMID: 34838156; NCT02034110). | 34838156 |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | glioblastoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in significant clinical improvement in a patient with epithelioid glioblastoma harboring BRAF V600E, however, her disease progressed after 3 months of therapy (PMID: 31217909). | 31217909 |
BRAF V600E | gastrointestinal stromal tumor | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | renal Wilms' tumor | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in regression in the metastatic disease of the liver, spleen, and peritoneum along with clinical symptom improvement in an adult patient with metastatic Wilms' tumor harboring BRAF V600E (PMID: 39234402). | 39234402 |
BRAF V600E BRAF over exp | melanoma | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line overexpressing BRAF V600E was resistant to the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in culture (PMID: 36622773). | 36622773 |
BRAF V600E | ganglioglioma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | Her2-receptor negative breast cancer | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a complete response in the liver and bone lesions with a progression-free survival of 9 months in a patient with metastatic ERBB2 (HER2)-negative, hormone receptor-positive breast cancer harboring BRAF V600E (PMID: 36531075). | 36531075 |
BRAF L485_P490del | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lymph node metastatic melanoma harboring BRAF L485_P490del and high CD274 (PD-L1) expression (TPS>=60%) experienced a partial response with regression of the target lesion after two cycles of second-line combination therapy with Tafinlar (dabrafenib) and Mekinist (trametinib), and at last follow up, demonstrated a sustained partial response and progression-free survival of at least 18 months (PMID: 36686670). | 36686670 |
BRAF V600E MAP2K1 F53C | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53C in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 G128V | melanoma | conflicting | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G128V in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 G128V | melanoma | conflicting | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 |
BRAF V600L | mucosal melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in complete remission in a patient with unresectable hypopharyngeal mucosal melanoma harboring BRAF V600L (PMID: 35709404). | 35709404 |
BRAF V600E | small intestine adenocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF del exon4-10 BRAF V600K | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a BRAF exon 4-10 deletion (reported as p55) variant was identified in the post-progression plasma ctRNA of a patient with metastatic melanoma harboring BRAF V600K who previously responded to treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33216826). | 33216826 |
BRAF V600E | lung papillary adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in regression of the lesions in the chest, abdomen and brain in a patient with lung papillary carcinoma harboring BRAF V600E but progression was observed 3 months later (PMID: 34178685). | 34178685 |
BRAF V47_D380del | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient developed progressive disease after initial response to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment, BRAF V47_D380del was identified as an acquired mutation in the progressing lesion along with mutations presented in both primary and progressing lesions, including BRAF V600E, PTEN G129E, CDKN2A/B loss, and TERT promoter mutations (PMID: 29171936). | 29171936 |
BRAF V600E MAP2K1 E203K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 36442478). | 36442478 |
BRAF V600E | intrahepatic cholangiocarcinoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an objective response rate of 38% in patients with advanced solid tumors harboring BRAF V600E, with a significantly greater tumor shrinkage observed in patients (n=4) with intrahepatic cholangiocarcinoma compared to the trial average ( -60% vs -35%, P=0.016) (PMID: 38109210). | 38109210 |
BRAF V600E | intrahepatic cholangiocarcinoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with intrahepatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to stable disease at 6 weeks, improvement of lung and liver lesions at 12 weeks after treatment, and response was maintained until disease progression in the liver was observed at 10 months (PMID: 33537843). | 33537843 |
BRAF V600E | intrahepatic cholangiocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
BRAF G469A BRAF L584P | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in decrease in metastatic lesions and a partial response with 94% reduction at three months and continued metabolic response at six months in a patient with metastatic melanoma harboring BRAF G469A and BRAF L584P (PMID: 31569065). | 31569065 |
BRAF V600R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response in one of two patients with melanoma harboring BRAF V600R, with a progression-free survival of 52.2 months in the responding patient (PMID: 36039514). | 36039514 |
BRAF V600E NRAS Q61K NRAS A146T | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to the combination therapy, Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 27797976). | 27797976 |
BRAF V600E MAP2K1 K59del | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E harboring MAP2K1 K59del in culture (PMID: 22389471). | 22389471 |
BRAF V600E MAP2K1 F53_Q58delinsL | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53_Q58delinsL in culture (PMID: 36442478). | 36442478 |
BRAF V600_W604delinsR | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 48 days, shrinkage of metastatic lesions, and decreased pleural effusion in a patient with advanced lung adenocarcinoma harboring BRAF V600_W604delinsR (PMID: 38766698). | 38766698 |
BRAF V600E | salivary gland cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with recurrent, unresectable, or metastatic salivary gland tumors harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | acinar cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in near complete metabolic remission at 5 months and persistent complete metabolic remission at 12 months in a patient with metastatic acinar cell carcinoma of unknown primary harboring BRAF V600E (PMID: 38820503). | 38820503 |
BRAF V600E MAP2K1 H119Y | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 H119Y in culture (PMID: 36442478). | 36442478 |
BRAF S365L BRAF V600E | lung papillary adenocarcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung papillary carcinoma harboring BRAF V600E who previously responded to Tafinlar (dabrafenib) and Mekinist (trametinib) treatment was found to have acquired BRAF S365L upon disease progression (PMID: 34178685). | 34178685 |
EML4 - ALK BRAF V600E | lung adenocarcinoma | no benefit | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20) and BRAF V600E developed progressive disease after 3 months of Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment (PMID: 36221356). | 36221356 |
BRAF G469A | lung adenocarcinoma | sensitive | Dabrafenib + Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
BRAF V600E MAP2K1 K57E | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57E in culture (PMID: 36442478). | 36442478 |
BRAF T599dup | ganglioglioma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in clinical improvement and tumor shrinkage with ongoing stable disease for at least 15 months in a pediatric patient with ganglioglioma harboring BRAF T599dup (PMID: 33637608). | 33637608 |
BRAF V600E | pancreatic cancer | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response in two patients with pancreatic cancer harboring BRAF V600E, including one patient with a progression-free survival (PFS) of at least 2 years on third-line therapy and another patient with a PFS of 48 weeks on second-line therapy (PMID: 34476331). | 34476331 |
BRAF V600D | pilocytic astrocytoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, single Tafinlar (dabrafenib) and subsequent Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease stablization in a patient with pilocytic astrocytoma harboring BRAF V600D (PMID: 28784858). | 28784858 |
BRAF L597R | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring BRAF L597R demonstrated clinical improvement and a tumor response at 13 weeks with resolution of hepatic metastasis and mediastinal lymphadenopathy when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and at the 12 month follow up remained on treatment, showing no disease progression (PMID: 32540409). | 32540409 |
BRAF V600E NRAS Q61R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) moderately inhibited tumor growth in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |
BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in clinical benefit that lasted for more than 14 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). | 29632053 |
BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | hairy cell leukemia | sensitive | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) demonstrated safety and resulted in an overall response rate of 89.1% (49/55; 36 complete responses, 13 partial responses) in patients with heavily pretreated recurrent/refractory hairy cell leukemia harboring BRAF V600E, with 24-month duration of response, progression-free-survival, and overall survival rates of 97.7%, 94.4% and 94.5%, respectively (PMID: 36108341; NCT02034110). | 36108341 |
BRAF G469V | lung adenocarcinoma | no benefit | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a previously treated lung adenocarcinoma patient harboring BRAF G469V demonstrated progression after 9 weeks of treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 32540409). | 32540409 |
BRAF V600K MAP2K1 P124L | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease progression within one month in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124L (PMID: 31980996). | 31980996 |
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 V600E | ovary epithelial cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E MAP2K1 E102_I103del | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E102_I103del in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T in culture (PMID: 36442478). | 36442478 |
BRAF K601E | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response lasting at least nine months with near-complete tumor regression in a patient with lung adenocarcinoma harboring BRAF K601E (PMID: 34590045). | 34590045 |
BRAF V600E | spermatic cord cancer | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a regression of the lung metastasis and progression-free survival of 6.5 months in a patient with undifferentiated sarcoma of the spermatic cord harboring BRAF V600E (PMID: 36157689). | 36157689 |
BRAF V600E | 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 colorectal cancer harboring BRAF V600E (PMID: 26392102). | 26392102 |
BRAF V600E | colorectal cancer | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
BRAF V600E | skin melanoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for cutaneous melanoma patients harboring a BRAF V600 mutation, such as BRAF V600E, as neoadjuvant or adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). | detail... |
BRAF V600E MAP2K1 F53L | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
BRAF V600D | ganglioglioma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response in a pediatric patient with ganglioglioma harboring BRAF V600D (PMID: 38844796; NCT03336931). | 38844796 |
BRAF V600E MAP2K1 I103_K104del | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103_K104del in culture (PMID: 36442478). | 36442478 |
BRAF K601E | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) treatment resulted in a partial response in a patient with metastatic melanoma harboring BRAF K601E, increased inhibition of Erk1/2 phosphorylation in a melanoma cell line expressing BRAF K601E in culture, and increased tumor growth inhibition in a patient-derived xenograft (PDX) model compared to Mekinist (trametinib) alone (PMID: 30248172). | 30248172 |
BRAF V600E MAP2K1 F53V | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53V in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F129L | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F129L in culture (PMID: 36442478). | 36442478 |
BRAF V600E | craniopharyngioma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response and progression-free survival of 1040 days in a patient with craniopharyngioma harboring BRAF V600E (PMID: 39143272). | 39143272 |
BRAF L597S | melanoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 89% (17/19) of tumors in a patient-derived xenograft (PDX) model harboring BRAF L597S, and treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a objective response with 34% tumor shrinkage in the patient from which the PDX model was derived from (PMID: 29903896). | 29903896 |
BRAF V600E | gastroesophageal junction adenocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | extrahepatic bile duct carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
BRAF G596R | colorectal cancer | 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 a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28947956). | 28947956 |
BRAF V600E MAP2K1 E203V | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203V in culture (PMID: 36442478). | 36442478 |
BRAF del exon4-8 BRAF V600E | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a BRAF exon 4-8 deletion variant (reported as p61) was identified in the post-progression plasma ctDNA of two patients with metastatic melanoma harboring BRAF V600E who previously responded to treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33216826). | 33216826 |
BRAF V600E | brain glioblastoma multiforme | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in tumor shrinkage after 2 months in a patient with epithelioid glioblastoma multiforme harboring BRAF V600E, who had progressed after resection, radiotherapy, and chemotherapy, and following an interruption in therapy due to toxicity demonstrated a partial response and remained progression-free for 19 months, prior to progressing 29 months after initiation of therapy (PMID: 33461766). | 33461766 |
BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). | 27312529 |
BRAF L597V | lung adenocarcinoma | sensitive | Dabrafenib + Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). | 22389471 |
BRAF V600E PTEN del | melanoma | decreased response | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and engineered via CRISPR-Cas9 to harbor a PTEN knockout demonstrated decreased sensitivity to treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) compared to cells with wild-type PTEN in culture (PMID: 38854737). | 38854737 |
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-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 | 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 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 V600E | ampulla of Vater adenocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as first-line therapy with good (ECOG 0-1; category 3) or poor (category 2B) performance status, or as subsequent therapy, for metastatic ampullary adenocarcinoma patients harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E MAP2K1 L115P | colorectal cancer | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). | 27312529 |
BRAF V600E MAP2K1 G128D | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G128D in culture (PMID: 36442478). | 36442478 |
BRAF V600_W604delinsDG | glioblastoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with epithelioid glioblastoma harboring BRAF V600_W604delinsDG responded to treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) with clinical improvement lasting 3 months (PMID: 39107839). | 39107839 |
BRAF V600E MAP2K1 F53I | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53I in culture (PMID: 36442478). | 36442478 |
BRAF V600E | Squamous Cell Carcinoma of Unknown Primary | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | salivary gland carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case report, combined Tafinlar (dabrafenib) and Mekinist (trametinib) treatment of a patient with salivary duct carcinoma harboring BRAF V600E resulted in a reduction of metastatic lesions and stable disease lasting 13 months followed by disease progression (PMID: 30323086). | 30323086 |
BRAF V600E | lung non-small cell carcinoma | sensitive | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634). | 27283860 detail... 27080216 detail... detail... 28919011 |
BRAF V600E | lung non-small cell carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as a first-line or subsequent therapy for advanced or metastatic non-small cell lung cancer patients harboring BRAF V600E mutations (NCCN.org). | detail... |
BRAF V600E | oncocytic carcinoma of the thyroid | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with thryoid Hürthle cell carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org). | detail... |
BRAF V600E | neuroendocrine tumor | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring BRAF V600E who have progressed on or following prior treatment (NCCN.org). | detail... |
BRAF V600E | neuroendocrine tumor | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
BRAF V600K | skin melanoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 mutation, such as BRAF V600K, as neoadjuvant or adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). | detail... |
BRAF V600E | pancreatic adenocarcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as first-line therapy for patients with locally advanced (category 2A) or metastatic (category 2B) pancreatic adenocarcinoma harboring BRAF V600E, and as subsequent-line therapy for patients with locally advanced, recurrent, or metastatic disease (category 2A) (NCCN.org). | detail... |
BRAF V600E | large cell neuroendocrine carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response in one of the lesions and a complete response in other lesions after 1 month in a patient with large cell neuroendocrine carcinoma of unknown primary harboring BRAF V600E (PMID: 36847048). | 36847048 |
BRAF G466V | lung non-small cell carcinoma | 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 a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 28947956). | 28947956 |
BRAF V600E MAP2K1 K57N | lung adenocarcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, MAP2K1 K57N was identified on the post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring BRAF V600E, who previously responded to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 32388065). | 32388065 |
BRAF V600E MAP2K1 I103N | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 36442478). | 36442478 |
BRAF N486_P490del | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in complete resolution of the pulmonary lesions and ongoing response after 6 months in a patient with metastatic lung adenocarcinoma harboring BRAF N486_P490del, who remained on treatment at 9 months (PMID: 38479107). | 38479107 |
BRAF V600E | esophagus squamous cell carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF T599dup | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical study, a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in partial responses in 4 patients with metastatic melanoma harboring BRAF T599dup, with one patient also harboring CTNNB1 I35T (PMID: 35319964). | 35319964 |
BRAF T599dup | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination resulted in partial metabolic remission within six weeks in a patient with metastatic melanoma harboring BRAF T599dup (PMID: 29494756). | 29494756 |
BRAF V600E BRAF K601_W604del | lung non-small cell carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, third-line Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response and progression-free survival of 155 days in a non-small cell lung cancer patient harboring BRAF V600E and K601_W604del (PMID: 35598548). | 35598548 |
BRAF V600E | gallbladder cancer | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including gallbladder cancer (NCCN.org). | detail... |
BRAF A598_T599insV | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in limited response in the primary tumor, but regression of the abdominal lymph node and groin metastases in a patient with metastatic melanoma harboring BRAF A598_T599insV, with a decrease in the variant allele frequency of BRAF A598_T599insV (PMID: 31824282). | 31824282 |
BRAF A598_T599insV | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a partial response within 4 weeks with a progression-free survival of 4.6 months in a patient with metastatic melanoma harboring BRAF A598_T599insV (PMID: 28800030). | 28800030 |
BRAF G469A BRAF W604C | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in stable disease indicated by decreased tumor density and disappearance of some metastatic lesions lasting 15 months in a patient with lung adenocarcinoma harboring BRAF G469A and W604C (PMID: 30926357). | 30926357 |
BRAF N581S NRAS Q61R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease stability with shrinkage of metastatic lesions in a melanoma patient harboring BRAF N581S and NRAS Q61R (PMID: 36217799). | 36217799 |
BRAF V600E | thyroid gland carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a partial response after 3 months in a patient with metastatic squamous cell carcinoma of the thyroid harboring BRAF V600E (PMID: 34956922). | 34956922 |
BRAF V600E | IDH-wildtype glioblastoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response lasting 9 months in a patient with metastatic MGMT unmethylated, IDH-wildtype glioblastoma harboring BRAF V600E along with amplification of MYC and TERT and loss of CDKN2A/B (PMID: 36825105). | 36825105 |
BRAF G469S | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in symptom improvement, reduced lymph node size, and decreased LDH levels in a patient with metastatic melanoma harboring BRAF G469S, with progression observed after three months (PMID: 31569065). | 31569065 |
BRAF V600E | anaplastic thyroid carcinoma | sensitive | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 61% (20/33; 3 complete responses, 17 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E, with 12-month duration of response rate of 50%, a median progression-free survival and overall survival of 6.7 and 14.5 months, respectively (PMID: 35026411; NCT02034110). | 35026411 detail... detail... detail... |
BRAF V600E | anaplastic thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for metastatic thyroid gland anaplastic carcinoma patients harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | anaplastic thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with advanced or metastatic thyroid gland anaplastic carcinoma harboring BRAF V600E (PMID: 31549998, PMID: 35491008; ESMO.org). | 31549998 detail... 35491008 |
BRAF V600E | anaplastic thyroid carcinoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). | 27697975 |
BRAF V600E | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response ongoing for at least 73 months in an elderly patient with lung adenocarcinoma harboring BRAF V600E (PMID: 39376796). | 39376796 |
BRAF V600E | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with a decrease in the size of the lung lesion in a patient with metastatic lung adenocarcinoma harboring BRAF V600E and germline BRCA L1908Rfs*2, who had previously progressed on several lines of therapy (PMID: 38715777). | 38715777 |
BRAF V600E | lung combined large cell neuroendocrine carcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 10 weeks in a patient with combined large cell neuroendocrine carcinoma harboring BRAF V600E, who remained recurrence-free for at least a year (PMID: 34969785). | 34969785 |
BRAF V600E MAP2K1 Q56_G61delinsR | melanoma | resistant | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56_G61delinsR in culture (PMID: 36442478). | 36442478 |
BRAF V600E CDKN2A R80* | skin melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic giant sarcomatoid melanoma harboring BRAF V600E and CDKN2A R80* achieved a partial response following four months of treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and reached a complete response with regression of lung and bone metastases after one year of treatment (PMID: 32922664). | 32922664 |
BRAF V600E IDH1 R132C | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with an overall survival of 51.1 months and a duration of treatment of 4.1 months in a melanoma patient harboring BRAF V600E and IDH1 R132C (PMID: 39500140). | 39500140 |
BRAF V600E | pilocytic astrocytoma | sensitive | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
BRAF V600E | pilocytic astrocytoma | sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the addition of Mekinist (trametinib) to treatment with Tafinlar (dabrafenib) resulted in a partial response in 3 pediatric patients with suprasellar pilocytic astrocytoma harboring BRAF V600E who all previously progressed on Tafinlar (dabrafenib) treatment alone (PMID: 39399174). | 39399174 |
BRAF V600E | cholangiocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with metastatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to a sustained metabolic response for six months (PMID: 33537843). | 33537843 |
BRAF V600E MAP2K1 V60E | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V60E in culture (PMID: 36442478). | 36442478 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT01726738 | Phase II | Dabrafenib + Trametinib | LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional Mutations | Completed | USA | 0 |
NCT03784014 | Phase III | Ceritinib Dabrafenib + Trametinib Capmatinib Durvalumab + Olaparib Nilotinib Futibatinib Trametinib Palbociclib Glasdegib Lapatinib | Molecular Profiling of Advanced Soft-tissue Sarcomas (MULTISARC) | Active, not recruiting | FRA | 0 |
NCT03919071 | Phase II | Dabrafenib + Trametinib | Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma | Recruiting | USA | 1 |
NCT02224781 | Phase III | Ipilimumab + Nivolumab Dabrafenib + Trametinib | Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma | Active, not recruiting | USA | 0 |
NCT02124772 | Phase I | Trametinib Dabrafenib + Trametinib | Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations | Completed | USA | GBR | FRA | CAN | AUS | 0 |
NCT02110355 | Phase Ib/II | KRT-232 + Trametinib Dabrafenib + KRT-232 + Trametinib Dabrafenib + Trametinib | A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma | Completed | USA | AUS | 0 |
NCT05299580 | Phase II | Dabrafenib + Trametinib | Dabrafenib and Trametinib in Circulating Free DNA BRAFV600 Mutated Metastatic Melanoma Patients: a Prospective Phase II, Open Label, Multicentre Study - (Bioliquid TAILOR Study - BIOTAILOR) | Withdrawn | ITA | 0 |
NCT02130466 | Phase Ib/II | Dabrafenib + Trametinib Pembrolizumab + Trametinib Dabrafenib + Pembrolizumab Dabrafenib + Pembrolizumab + Trametinib | A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022/KEYNOTE-022) | Completed | 0 | |
NCT05159245 | Phase II | Vemurafenib Tepotinib Vismodegib Apalutamide Alectinib Regorafenib Entrectinib Pertuzumab + Trastuzumab Pemigatinib Atezolizumab Cobimetinib Dabrafenib + Trametinib Dabrafenib Trametinib Abemaciclib | The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs (FINPROVE) | Recruiting | FIN | 0 |
NCT05182931 | Phase II | Dabrafenib + Trametinib Trametinib | A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study) (I-FIRST) | Recruiting | AUS | 0 |
NCT02684058 | Phase II | Dabrafenib + Trametinib | Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG | Completed | USA | SWE | NLD | ITA | ISR | GBR | FRA | FIN | ESP | DNK | DEU | CZE | CHE | CAN | BRA | BEL | AUS | ARG | 2 |
NCT04940052 | Phase III | Dabrafenib + Trametinib | Study of Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer | Active, not recruiting | USA | TUR | CAN | BRA | ARG | 6 |
NCT04527549 | Phase II | Dabrafenib + Trametinib Dabrafenib + Hydroxychloroquine + Trametinib | Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma | Terminated | USA | 0 |
NCT03551626 | Phase III | Dabrafenib + Trametinib | Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes (COMBI-APlus) | Completed | TUR | SWE | SVN | SVK | POL | NOR | LVA | LTU | ITA | ISR | HUN | GRC | GBR | FRA | FIN | CZE | CAN | BRA | AUS | ARG | 3 |
NCT02034110 | Phase II | Dabrafenib + Trametinib | Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers | Completed | USA | SWE | NOR | NLD | ITA | FRA | ESP | DNK | DEU | CAN | BEL | AUT | 2 |
NCT03091257 | Phase I | Dabrafenib + Trametinib Dabrafenib Trametinib | A Study of Dabrafenib and/or Trametinib in Patients With Relapsed and/or Refractory Multiple Myeloma | Recruiting | USA | 0 |
NCT01682083 | Phase III | Dabrafenib + Trametinib | Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD). (COMBI-AD) | Completed | USA | SWE | POL | NZL | NOR | NLD | ITA | ISR | GRC | GBR | FRA | ESP | DNK | DEU | CZE | CHE | CAN | BRA | BEL | AUT | AUS | ARG | 3 |
NCT02039947 | Phase II | Dabrafenib + Trametinib | Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain | Completed | USA | ITA | FRA | ESP | DEU | CAN | AUS | 0 |
NCT01701037 | Phase II | Dabrafenib + Trametinib Dabrafenib | Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery | Terminated | USA | 0 |
NCT02367859 | Phase II | Dabrafenib + Trametinib | Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma | Completed | USA | 0 |
NCT02967692 | Phase III | Dabrafenib + Spartalizumab + Trametinib Dabrafenib + Trametinib | A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (COMBI-i) | Completed | USA | SWE | POL | NOR | NLD | ITA | ISR | HUN | GRC | GBR | FRA | ESP | DNK | DEU | CZE | CHE | CAN | BRA | BGR | BEL | AUT | AUS | ARG | 6 |
NCT02231775 | Phase II | Dabrafenib + Trametinib | Combi-Neo Study for Stage IV Melanoma | Active, not recruiting | USA | 0 |
NCT05525273 | Phase II | Dabrafenib + Trametinib | Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma (Swecranio) | Recruiting | SWE | 0 |
NCT03563729 | Phase II | Pembrolizumab Binimetinib + Encorafenib Ipilimumab + Nivolumab Dabrafenib + Trametinib | Melanoma Metastasized to the Brain and Steroids (MEMBRAINS) | Recruiting | DNK | 0 |
NCT04059224 | Phase II | Dabrafenib + Trametinib | TraMel-WT: A Trial of Trametinib in Patients With Advanced Pretreated BRAFV600 Wild-type Melanoma (TraMel-WT) | Completed | BEL | 0 |
NCT01619774 | Phase II | Dabrafenib + Trametinib | An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor | Completed | USA | 0 |
NCT04619316 | Phase II | Dabrafenib + Trametinib Trametinib | Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition (ERRITI) | Recruiting | DEU | 0 |
NCT01989585 | Phase Ib/II | Dabrafenib + Navitoclax + Trametinib Dabrafenib + Trametinib | Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma | Active, not recruiting | USA | 0 |
NCT06079333 | Phase II | Dabrafenib + Trametinib | NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study) (NEO-ATACT) | Recruiting | NLD | 0 |
NCT03975829 | FDA approved | Dabrafenib + Trametinib | Pediatric Long-Term Follow-up and Rollover Study | Active, not recruiting | USA | SWE | NLD | ITA | ISR | GBR | FRA | FIN | ESP | DNK | DEU | CZE | CAN | BRA | BEL | AUS | ARG | 2 |
NCT03340506 | FDA approved | Trametinib Dabrafenib Dabrafenib + Trametinib | Dabrafenib and/or Trametinib Rollover Study | Recruiting | USA | NLD | HUN | FRA | ESP | DNK | DEU | AUT | ARG | 3 |
NCT01978236 | Phase II | Dabrafenib + Trametinib Dabrafenib | Dabrafenib/Trametinib, BRAF or BRAF AND MEK Pre-op With BRAF and MEK Post-op, Phase IIB, Melanoma With Brain Mets,Biomarkers and Metabolites | Terminated | USA | AUS | 0 |
NCT04817956 | Phase II | Ceritinib Melphalan Cobimetinib + Vemurafenib Alectinib Pemigatinib Entrectinib Bortezomib Dostarlimab-gxly Atezolizumab Alpelisib Atezolizumab + Bevacizumab Olaparib Selpercatinib Capmatinib Dactinomycin Dabrafenib + Trametinib Vismodegib Niraparib Imatinib Pertuzumab/trastuzumab/hyaluronidase-zzxf | Improving Public Cancer Care by Implementing Precision Medicine in Norway (IMPRESS-N) | Recruiting | NOR | 0 |
NCT03975231 | Phase I | Dabrafenib + Trametinib | Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer | Recruiting | USA | 0 |
NCT03244956 | Phase II | Trametinib Dabrafenib + Trametinib | Efficacy of MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer (MERAIODE) | Unknown status | FRA | 0 |
NCT01723202 | Phase II | Dabrafenib + Trametinib Dabrafenib | Dabrafenib With or Without Trametinib in Treating Patients With Recurrent Thyroid Cancer | Unknown status | USA | 0 |
NCT01336634 | Phase II | Dabrafenib Dabrafenib + Trametinib | Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. | Completed | USA | NOR | NLD | ITA | GBR | FRA | ESP | DEU | 3 |
NCT02465060 | Phase II | Nivolumab + Relatlimab Dabrafenib + Trametinib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Active, not recruiting | USA | 2 |
NCT02196181 | Phase II | Dabrafenib + Trametinib | Dabrafenib and Trametinib for the Treatment of Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
NCT04310397 | Phase II | Dabrafenib + Trametinib Dabrafenib + Spartalizumab + Trametinib | Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma | Terminated | USA | 0 |
NCT02974803 | Phase II | Dabrafenib + Trametinib | Concurrent Dabrafenib + Trametinib With Sterotactic Radiation in BRAF Mutation-Positive Malignant Melanoma and Brain Metastases | Terminated | CAN | 0 |