Therapy Detail
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| Therapy Name | Trametinib |
| Synonyms | |
| Therapy Description |
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). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| 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). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E NRAS Q61R | melanoma | resistant | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R was resistant to treatment with Mekinist (trametinib) (PMID: 37729428). | 37729428 |
| BRAF V600E MAP2K1 Q58* | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q58* in culture (PMID: 36442478). | 36442478 |
| BRAF mutant | colorectal cancer | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF V600K NRAS Q61K | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| MAP2K1 K57E | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57E in culture (PMID: 36442478). | 36442478 |
| FGFR1 amp NRAS amp | lung non-small cell carcinoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification were resistant to Mekinist (trametinib) in culture (PMID: 28630215). | 28630215 |
| BRAF V600E BRAF over exp | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line overexpressing BRAF V600E was resistant to Mekinist (trametinib) in culture (PMID: 36622773). | 36622773 |
| HRAS mutant | endometrial cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human endometrial cancer cells harboring mutant HRAS in culture (PMID: 26343583). | 26343583 |
| CSF3R T618I | hematologic cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited colony formation in transformed bone marrow cells expressing CSF3R T618I in culture (PMID: 29572350). | 29572350 |
| BRAF V600E MAP2K1 P293S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P293S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 N382H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N382H in culture (PMID: 36442478). | 36442478 |
| NRAS Q61L NRAS mut | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| MAP2K1 C121S | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 C121S in culture (PMID: 36442478). | 36442478 |
| MAP2K1 C121S MAP2K1 P124R | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) resulted in a partial response after two months of treatment in a patient with melanoma harboring MAP2K1 C121S and MAP2K1 P124R (PMID: 36901951). | 36901951 |
| BRAF K601E | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). | 22798288 |
| BRAF V600K | melanoma | sensitive | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| NRAS Q61R | acute biphenotypic leukemia | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a clinical study, Mekinist (trametinib) treatment was well tolerated and led to an initial decrease of peripheral blasts in a pediatric patient with mixed phenotype acute leukemia harboring NRAS Q61R who had previously undergone a stem cell transplant, but patient experienced progressive disease after 2 months, and died soon after (PMID: 33563661; NCT02670525). | 33563661 |
| BRAF D594G | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF D594G (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF D594G | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring BRAF D594G and TP53 H193L demonstrated stable disease for two months when treated with Mekinist (trametinib), but progressed after four months (PMID: 32540409). | 32540409 |
| BRAF V600E MAP2K1 F53S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53S in culture (PMID: 28986383). | 28986383 |
| MAP2K1 L98_K104delinsQ | lymphatic system cancer | predicted - resistant | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with Langerhans cell histiocytosis harboring MAP2K1 L98_K104delinsQ demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 29768711). | 29768711 |
| MAP2K1 L115P | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 L115P were resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| BRAF L485_P490delinsFS | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsFS in culture (PMID: 37656784). | 37656784 |
| MAP2K1 Q56_G61delinsR | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 Q56_G61delinsR in culture (PMID: 36442478). | 36442478 |
| BRAF V487_P492delinsA | pancreatic cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). | 26732095 |
| MAP2K1 V60E | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Mekinist (trametinib) in culture (PMID: 24265153). | 24265153 |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P162S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K1 P162S in culture (PMID: 24265154). | 24265154 |
| BRAF V600E NRAS A146T | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF G466A | gastrointestinal system cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gastrointestinal system cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 |
| BRAF V600E | thyroid cancer | predicted - sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| NRAS mutant | leukemia | predicted - sensitive | Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). | detail... |
| BRAF G466E HRAS Q61K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF V600E MAP2K1 Y134C | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 Y134C | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C in culture (PMID: 28986383). | 28986383 |
| PIK3CA Q546K | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). | 26627007 |
| MAP2K1 E41_L54del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 |
| BRAF V600E MAP2K1 E203K | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 E203K | melanoma | conflicting | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 E203K | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF D594G | gastrointestinal system cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 4 patients with gastrointestinal system cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). | 31924734 |
| NRAS Q61H | rhabdomyosarcoma | no benefit | Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and viability in rhabdomyosarcoma cell lines harboring NRAS Q61H in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). | 34737198 |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with BRAF V600E positive advanced solid tumors other than melanoma, thyroid cancer, or colorectal cancer, with a median duration of response of 25.1 months, and a disease control rate of 75.9% (22/29) (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with pleomorphic xanthoastrocytoma achieved a partial response lasting 7.2 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF N581S | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF N581S (PMID: 31924734; NCT02465060). | 31924734 |
| MAP2K1 F53C | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F53C in culture (PMID: 36442478). | 36442478 |
| HRAS Q61K PTEN dec exp | rhabdomyosarcoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, decreasing Pten expression through shRNA knockdown in a rhabdomyosarcoma cell line harboring HRAS Q61K conferred resistance to Mekinist (trametinib) treatment in culture (PMID: 36322002). | 36322002 |
| BRAF V600E MAP2K1 D136N | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D136N in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| MAP2K1 E41_L54del | lung cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed human lung cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 |
| FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
| BRAF V600E MAP2K1 P264S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264S in culture (PMID: 36442478). | 36442478 |
| MAP2K1 K57N | lung non-squamous non-small cell carcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in a radiographic response with a decrease in the size of multiple metastatic sites in a patient with non-squamous non-small cell lung cancer harboring MAP2K1 K57N (PMID: 36455195). | 36455195 |
| BRAF L597S | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597S (PMID: 22798288). | 22798288 |
| BRAF V600E MAP2K1 S86A | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S86A in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S200Y | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S200Y in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 G79V | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G79V in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 I99_K104del | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I99_K104del was resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| MAP2K1 I103_K104del | Advanced Solid Tumor | decreased response | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing MAP2K1 I103_K104del were less sensitive to Mekinist (trametinib) compared to similar mutations in the negative regulatory domain of the Map2k1 protein in culture (PMID: 32641410). | 32641410 |
| BRAF V600E MAP2K1 I99T | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99T demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 |
| BRAF G464E | sarcomatoid carcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 6.9 months in a patient with spindle cell carcinoma harboring a BRAF G464E (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G466E HRAS G13R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and BRAF G466E were sensitive to Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 39152269). | 39152269 |
| BRAF L597Q | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, first-line treatment with Mekinist (trametinib) resulted in a partial response lasting 6.2 months in a melanoma patient harboring BRAF L597Q, with 33% tumor shrinkage (PMID: 24933606). | 24933606 |
| BRAF L597Q | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, Mekinist (trametinib) treatment resulted in an objective response rate of 33% (3/9, all partial responses) and a median progression-free survival (PFS) of 7.3 months in melanoma patients harboring BRAF fusions or non-V600 BRAF mutations, including a partial response with a tumor reduction of 38% and PFS ongoing 8.3 months in a patient harboring BRAF L597Q (PMID: 33861486; NCT02296112). | 33861486 |
| BRAF mutant | pancreatic adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | non-Hodgkin lymphoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF G464V | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G464V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 Q56_G61delinsR | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56_G61delinsR was resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 G276W | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G276W in culture (PMID: 36442478). | 36442478 |
| BRAF V600X | low grade glioma | predicted - sensitive | Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, Mekinist (trametinib) treatment demonstrated a manageable safety profile in pediatric patients with BRAF V600-mutant low grade glioma, and resulted in an objective response rate of 15.4% (2/13, all partial responses), a clinical benefit rate of 61.5% (8/13), a median progression-free survival of 16.4 months, and median duration of response not reached (PMID: 36375115; NCT02124772). | 36375115 |
| BRAF V600E MAP2K1 I204T | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I204T in culture (PMID: 36442478). | 36442478 |
| NRAS wild-type | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, an NRAS wild-type melanoma cell line demonstrated inhibition of cell growth when treated with Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| MAP2K1 L63_D67del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 L63_D67del in culture (PMID: 36442478). | 36442478 |
| MAP2K1 F53L | colorectal cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F53L demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in decreased cell viability (PMID: 26582713). | 26582713 |
| BRAF L597V | endometrial adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 7.9 months in a patient with endometrial adenocarcinoma harboring BRAF L597V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 R96K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R96K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 V127M | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V127M in culture (PMID: 36442478). | 36442478 |
| BRAF A598_T599insV | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, Mekinist (trametinib) treatment resulted in clinical benefit in six of nine melanoma patients harboring BRAF fusions or non-V600 BRAF mutations, including stable disease lasting 7.3 months with a tumor reduction of 8% in a patient harboring BRAF A598_T599insV, who also harbored KIT M541L (PMID: 33861486; NCT02296112). | 33861486 |
| MAP2K1 K57T | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57T in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | acute myeloid leukemia | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 C121S | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 C121S | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 C121S | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Mekinist (trametinib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 S150F | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S150F in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S327T | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S327T in culture (PMID: 36442478). | 36442478 |
| HRAS mutant | transitional cell carcinoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human urinary transitional cell carcinoma cells harboring mutant HRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF N486_P490del | lymphatic system cancer | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). | 32991018 |
| MAP2K1 F53I | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F53I in culture (PMID: 36442478). | 36442478 |
| MAP2K1 L42_K57del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 L42_K57del in culture (PMID: 36442478). | 36442478 |
| BRAF G596R | colorectal cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced Erk signaling and inhibited proliferation of a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). | 28783719 |
| BRAF V600E MAP2K1 P193S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P193S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | sarcoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 V258I | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V258I in culture (PMID: 36442478). | 36442478 |
| BRAF L485_P490delinsF | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsF in culture (PMID: 37656784). | 37656784 |
| BRAF G466V NRAS Q61K | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF L597X | melanoma | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with BRAF L597 mutations (NCCN.org). | detail... |
| BRAF V600E MAP2K1 P387S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P387S in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | ovarian cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 G294E | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G294E in culture (PMID: 36442478). | 36442478 |
| MAP2K1 E203K | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 E203K in culture (PMID: 36442478). | 36442478 |
| MAP2K1 Q56P | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
| MAP2K1 F53L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 F53L in culture (PMID: 32641410). | 32641410 |
| MAP2K1 F53L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 Y229H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y229H in culture (PMID: 36442478). | 36442478 |
| PIK3CA H1047R | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
| MAP2K1 F129L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F129L in culture (PMID: 36442478). | 36442478 |
| MAP2K1 L42F | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 L42F in culture (PMID: 32641410). | 32641410 |
| PIK3CA H1047L | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
| MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in complete remission of cutaneous lesions and resolution of the pituitary gland enlargement and associated symptoms in a patient with Langerhans cell histiocytosis harboring MAP2K1 E102_I103del (PMID: 35172489). | 35172489 |
| MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in symptom improvement, resolution of the partial pneumothorax, and reduction in cystic lesions in a patient with pulmonary Langerhans cell histiocytosis harboring MAP2K1 E102_I103del (PMID: 29694792). | 29694792 |
| MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with Mekinist (trametinib) resulted in complete remission in a pediatric patient with Langerhans cell histiocytosis harboring MAP2K1 E102_I103del, with treatment ongoing for at least 10 months (PMID: 36730444). | 36730444 |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| PIK3CA Q546K | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA Q546K in culture (PMID: 26627007). | 26627007 |
| BRAF L597R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). | 22798288 |
| MAP2K1 K57N | lymphatic system cancer | sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 K57N mutation had a sustained clinical response to Mekinist (trametinib) for over 6 months (PMID: 26566875). | 26566875 |
| MAP2K1 Q56P | stomach cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a gastric cancer cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
| PIK3CA E545K | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). | 26627007 |
| NRAS Q61R | gastrointestinal neuroendocrine tumor | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability, proliferation, and migration of a cell line derived from a pediatric gastroenteropancreatic neuroendocrine-like tumor patient-derived xenograft (PDX) model harboring NRAS Q61R in culture and inhibited tumor growth and increased survival compared to treatment with vehicle in a patient-derived xenograft (PDX) cell line model (PMID: 38959709). | 38959709 |
| NRAS Q61H | mucosal melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment inhibited viability of patient-derived mucosal melanoma cells harboring NRAS Q61H in culture (PMID: 39001563). | 39001563 |
| NRAS Q61H | mucosal melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited downstream signaling and decreased viability of a mucosal melanoma cell line harboring NRAS Q61H in culture (PMID: 29054983). | 29054983 |
| BRAF mutant | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| MAP2K1 G128D | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 G128D in culture (PMID: 36442478). | 36442478 |
| MAP2K1 G128D | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation and decreased cell size in a cell line expressing MAP2K1 G128D (PMID: 34726260). | 34726260 |
| NRAS mutant | liver cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF V600K MAP2K1 P124Q | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). | 25370473 |
| CSF3R N610H | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing CSF3R N610H in culture (PMID: 30348809). | 30348809 |
| BRAF L485_P490delinsY | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). | 37656784 |
| BRAF V600E MAP2K1 P326H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P326H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | triple-receptor negative breast cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment inhibited Mapk signaling and viability in a triple-negative breast cancer cell line harboring BRAF V600E in culture (PMID: 36011019). | 36011019 |
| BRAF G466V | Advanced Solid Tumor | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with tumor of unknown primary harboring BRAF G466V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E | lung adenocarcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with lung adenocarcinoma, 1 achieved a partial response with an ongoing progression-free survival (PFS) at 32.5 mo, 3 patients had stable disease for 15.6, 6.6, and 3.6 mo, and an additional unevaluable patient achieved an 81% reduction of measured lesions and a PFS of 12.7 mo (PMID: 32758030; NCT02465060). | 32758030 |
| PIK3CA N345K | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
| BRAF G466V | colorectal cancer | sensitive | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 |
| BRAF N486_P490del | ovarian cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26732095). | 26732095 |
| BRAF N486_P490del | ovarian cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| NRAS mut PIK3CA H1047R | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing PIK3CA H1047R demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| BRAF V600E | diffuse leptomeningeal glioneuronal tumor | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in a partial response in the brain and stable disease in the spine in a pediatric patient with diffuse leptomeningeal glioneuronal tumor harboring BRAF V600E (PMID: 39399174). | 39399174 |
| BRAF mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 L235H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L235H in culture (PMID: 36442478). | 36442478 |
| PIK3CA G1049R | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). | 26627007 |
| BRAF V600E MAP2K1 R47Q | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R47Q in culture (PMID: 36442478). | 36442478 |
| CSF3R N610S | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing CSF3R N610S in culture (PMID: 30348809). | 30348809 |
| MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 Q56P in culture (PMID: 32641410). | 32641410 |
| MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 Q56P in culture (PMID: 36442478). | 36442478 |
| BRAF S363F BRAF K601E | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| MAP2K1 K59del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K59del in culture (PMID: 36442478). | 36442478 |
| PIK3CA H1047R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA H1047R in culture (PMID: 26627007). | 26627007 |
| BRAF V600E MAP2K1 V154I | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V154I in culture (PMID: 36442478). | 36442478 |
| PIK3CA G1049R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA G1049R in culture (PMID: 26627007). | 26627007 |
| BRAF V600E MAP2K1 P264L | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264L in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 K4N | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K4N in culture (PMID: 36442478). | 36442478 |
| BRAF G466A | prostate cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| HRAS G13R | thyroid cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
| BRAF V600E MAP2K1 R49C | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R49C in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D67Y | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67Y in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). | 22389471 |
| BRAF L597V | lung adenocarcinoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF K601E | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). | 28344857 |
| BRAF K601E | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). | 23248257 |
| BRAF K601E | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, treatment with Mekinist (trametinib) resulted in a clinical benefit rate of 75% (3/4) in melanoma patients harboring BRAF K601E, with two partial responses each lasting 2.5 and 5.5 months, and one with stable disease lasting 3.6 months with a 27% reduction in tumor mass (PMID: 24933606). | 24933606 |
| MAP2K1 F53L | histiocytic sarcoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in resolution of symptoms within 3 days and a durable complete response for over 2 years in a patient with histiocytic sarcoma harboring MAP2K1 F53L (PMID: 29768143). | 29768143 |
| BRAF V600E MAP2K1 V93F | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V93F in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | lymphoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF N581S | female reproductive organ cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecologic cancer harboring BRAF N581S (PMID: 31924734; NCT02465060). | 31924734 |
| MAP2K1 T55P | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 T55P in culture (PMID: 32641410). | 32641410 |
| BRAF V600E MAP2K1 A132V | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A132V in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R291K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R291K in culture (PMID: 36442478). | 36442478 |
| MAP2K1 H119Q | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 H119Q in culture (PMID: 32641410). | 32641410 |
| CTNNB1 mut NRAS mut | liver cancer | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human liver cancer cells harboring mutant NRAS and mutant CTNNB1 were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| NRAS mutant | melanoma | sensitive | Trametinib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292; NCT00687622). | 22805292 |
| NRAS mutant | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 |
| BRAF G466V | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). | 28783719 |
| MAP2K1 K57N | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57N in culture (PMID: 36442478). | 36442478 |
| MAP2K1 K57N | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 K57N in culture (PMID: 32641410). | 32641410 |
| MAP2K1 mutant | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| BRAF V600E MAP2K1 L63_D67del | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L63_D67del in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| CDKN2A loss | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line with CDKN2A loss demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in inhibition of cell growth (PMID: 27488531). | 27488531 |
| BRAF N486_P490del | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| BRAF G466A | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 1 and stable disease in 2 patients with lung adenocarcinoma harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| MAP2K1 K57_G61del | lymphatic system cancer | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a pediatric patient with Langerhans cell histiocytosis harboring MAP2K1 K57_G61del treated with Mekinist (trametinib) achieved a rapid complete response and had no active disease over 22 months of treatment (PMID: 32991018). | 32991018 |
| BRAF K601E | prostate adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in a near partial response in a patient with prostate adenocarcinoma harboring BRAF K601E until disease progression at 9.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF mutant | lymphoma | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G469A | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) induced apoptosis and inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 25706985). | 25706985 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K was resistant to Mekinist (trametinib) in culture (PMID: 36622773). | 36622773 |
| BRAF V600E MAP2K1 S331R | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S331R in culture (PMID: 36442478). | 36442478 |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 |
| MAP2K1 H119Y | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 H119Y in culture (PMID: 32641410). | 32641410 |
| BRAF D594G | prostate cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with prostate cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). | 31924734 |
| MAP2K1 I99_K104del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 I99_K104del were resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| MAP2K1 F129L | ovarian serous carcinoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, MAP2K1 F129L was identified in a low grade serous ovarian cancer cell line that developed resistance to treatment with Mekinist (trametinib) in culture (PMID: 36198031). | 36198031 |
| BRAF V600E MAP2K1 R49L | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R49L in culture (PMID: 36442478). | 36442478 |
| PIK3CA E542K | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA E542K in culture (PMID: 26627007). | 26627007 |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 5 patients with low grade serous ovarian carcinoma, 4 achieved a partial response (PR), 1 had stable disease, 3 of the PRs lasted over 12 months (PMID: 32758030; NCT02465060). | 32758030 |
| MAP2K1 K57_G61del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57_G61del in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | intrahepatic cholangiocarcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with intrahepatic cholangiocarcinoma, 3 achieved a partial response, with individual progression-free survival of 12.8, 9.1, and 29.4 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E MAP2K1 G176S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G176S in culture (PMID: 36442478). | 36442478 |
| EML4 - RET | lung adenocarcinoma | conflicting | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a patient-derived lung adenocarcinoma cell line harboring EML4-RET was resistant to treatment with Mekinist (trametinib), demonstrating decreased cell proliferation in culture, but led to delayed tumor growth in a cell line xenograft model (PMID: 33795352). | 33795352 |
| BRAF mutant | Advanced Solid Tumor | no benefit | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 M146I | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 M146I in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 N345T | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N345T in culture (PMID: 36442478). | 36442478 |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). | 37656784 |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY in culture (PMID: 26732095). | 26732095 |
| NRAS mutant | transitional cell carcinoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 R49H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R49H in culture (PMID: 36442478). | 36442478 |
| BRAF G469E | breast ductal carcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, only 1 patient with breast ductal carcinoma harboring BRAF G469E achieved a partial response with a tumor shrinkage of 50% at 4 months, but the patient died suddenly at 4.3 months with no disease progression (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 I99G | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99G demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 |
| NRAS Q61K | neuroblastoma | predicted - sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, neuroblastoma cell lines either harboring or expressing NRAS Q61K demonstrated moderate growth inhibition in culture and in cell line xenograft models when treated with Mekinist (trametinib) (PMID: 32586982). | 32586982 |
| CDKN2A mut NRAS act mut | acute lymphoblastic leukemia | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| PIK3CA E545K | diffuse midline glioma, H3 K27M-mutant | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of mouse glioma cells expressing H3.1 K28M (reported as H3.1 K27M), ACVR1 G328V, and PIK3CA E545K in culture (PMID: 37011011). | 37011011 |
| MAP2K1 F53_Q58delinsL | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F53_Q58delinsL in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | peritoneal serous papillary adenocarcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with mucinous-papillary serous adenocarcinoma of the peritoneum achieved a partial response (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E MAP2K1 K57_G61del | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57_G61del in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R108Q | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R108Q in culture (PMID: 36442478). | 36442478 |
| NRAS Q61R | acral lentiginous melanoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment inhibited viability of patient-derived acral melanoma cells harboring NRAS Q61R in culture (PMID: 39001563). | 39001563 |
| MAP2K1 E102_I103del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing MAP2K1 E102_I103del were less sensitive to Mekinist (trametinib) compared to to similar mutations in the negative regulatory domain of the Map2k1 protein in culture (PMID: 32641410). | 32641410 |
| MAP2K1 E102_I103del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 E102_I103del were resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| MAP2K1 R49L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 R49L in culture (PMID: 36442478). | 36442478 |
| MAP2K1 G61_D65del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 G61_D65del in culture (PMID: 36442478). | 36442478 |
| BRAF fusion | skin melanoma | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with BRAF fusions (NCCN.org). | detail... |
| NRAS Q61R | urinary bladder cancer | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased tumor weight of a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). | 34554931 |
| BRAF V600E MAP2K1 W247* | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 W247* in culture (PMID: 36442478). | 36442478 |
| BRAF wild-type | melanoma | sensitive | Trametinib | Phase I | Actionable | In a Phase I study, 10% (4/39) of wild-type BRAF melanoma patients had a partial response to Mekinist (trametinib) (PMID: 22805292; NCT00687622). | 22805292 |
| BRAF V600E MAP2K1 P124L | melanoma | decreased response | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF mut RB1 loss | melanoma | decreased response | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| BRAF G469V | osteosarcoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with osteosarcoma of the renal pelvis harboring BRAF G469V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 A14S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A14S in culture (PMID: 36442478). | 36442478 |
| NRAS G75_E76insDSAMRDQYMRTG | myelodysplastic/myeloproliferative neoplasm | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) decreased the accumulation of immature myeloid cells in a zebrafish model of myelodysplastic/myeloproliferative neoplasm harboring NRAS G75_E76insDSAMRDQYMRTG (PMID: 38522505). | 38522505 |
| BRAF R506_K507insLLR | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) treatment resulted in decreased Erk signaling in cultured cells expressing BRAF R506_K507insLLR and inhibited tumor growth in cell line xenograft models (PMID: 34108213). | 34108213 |
| HRAS Q61K | rhabdomyosarcoma | no benefit | Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and viability in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). | 34737198 |
| BRAF V504_R506dup | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) treatment resulted in decreased Erk signaling in cultured cells expressing BRAF V504_R506dup and inhibited tumor growth in cell line xenograft models (PMID: 34108213). | 34108213 |
| BRAF V504_R506dup | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) treatment resulted in decreased Erk1/2 phosphorylation in transformed cells expressing BRAF V504_R506dup in culture (PMID: 30575814). | 30575814 |
| BRAF fusion | prostate cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring a BRAF fusion (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 A106T | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A106T in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | central nervous system cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF V600E MAP2K1 D336H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D336H in culture (PMID: 36442478). | 36442478 |
| BRAF D594G | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF D594G in culture (PMID: 28783719). | 28783719 |
| NRAS mutant | lung adenocarcinoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| FGFR2 K660N | estrogen-receptor positive breast cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 K660N in culture (PMID: 32723837). | 32723837 |
| BRAF V600E MAP2K1 M94I | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 M94I in culture (PMID: 36442478). | 36442478 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a pancreatic ductal adenocarcinoma patient-derived organoid model harboring BRAF N486_P490del was sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 37463056). | 37463056 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). | 29903880 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with Mekinist (trametinib) (PMID: 34011980). | 34011980 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| DNMT3A R882H NRAS G12D | acute myeloid leukemia | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). | 31164355 |
| FGFR2 M538I | estrogen-receptor positive breast cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 M538I in culture (PMID: 32723837). | 32723837 |
| PIK3CA N345K | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
| MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 |
| BRAF V600E | histiocytic sarcoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with histiocytic sarcoma of the brain achieved a partial response with an ongoing progression-free survival at 20.9 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF T599dup | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited downstream signaling and viability in transformed cells expressing BRAF T599dup in culture (PMID: 38662982). | 38662982 |
| BRAF L514V BRAF V600E | melanoma | decreased response | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 |
| BRAF G469A | lung adenocarcinoma | conflicting | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF G469A | lung adenocarcinoma | conflicting | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF G469A, who remained on therapy for 20.4 months without progression (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF F247L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Mekinist (trametinib) in culture (PMID: 28512244). | 28512244 |
| MAP2K1 L177M | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 L177M in culture (PMID: 32641410). | 32641410 |
| BRAF V600E MAP2K1 S231L | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S231L in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 E367K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E367K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 I111S | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I111S in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| BRAF V600E MAP2K1 P306H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P306H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E/K | melanoma | sensitive | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF V600E/K | melanoma | sensitive | Trametinib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292; NCT00687622). | 22805292 |
| BRAF V600E MAP2K1 G61_D65del | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G61_D65del in culture (PMID: 36442478). | 36442478 |
| MAP2K1 P105_A106del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 P105_A106del were resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| MAP2K1 P105_A106del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing MAP2K1 P105_A106del were less sensitive to Mekinist (trametinib) compared to similar mutations in the negative regulatory domain of the Map2k1 protein in culture (PMID: 32641410). | 32641410 |
| BRAF V600E MAP2K1 R201C | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201C in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 L54P | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L54P in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 I99M | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99M demonstrated sensitivity to Mekinist (trametinib) treatment similar to cells expressing wild-type MAP2K1 in culture (PMID: 31925410). | 31925410 |
| PIK3CA E545K | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA E545K in culture (PMID: 26627007). | 26627007 |
| BRAF V600E MAP2K1 S72G | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S72G in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D67N | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 D67N | melanoma | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N in culture (PMID: 36442478). | 36442478 |
| MAP2K1 Q58_E62del | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 Q58_E62del in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R349K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R349K in culture (PMID: 36442478). | 36442478 |
| BRAF L597Q | colon adenocarcinoma | predicted - sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). | 31704811 |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 S212N | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S212N in culture (PMID: 36442478). | 36442478 |
| BRAF G469A | invasive bladder transitional cell carcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in a partial response and stable disease lasting more than 18 months in a patient with muscle-invasive urothelial bladder carcinoma harboring BRAF G469A (PMID: 39224677). | 39224677 |
| NRAS mut PIK3CA E545K | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines expressing PIK3CA E545K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| NRAS mutant | autonomic nervous system neoplasm | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 |
| BRAF D594N | female reproductive organ cancer | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecological cancer harboring BRAF D594N (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 R201H | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D351G | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D351G in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
| BRAF V600E MAP2K1 I111N | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 F53_Q58delinsL | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53_Q58delinsL was resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | melanoma | sensitive | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF L597S | melanoma | predicted - sensitive | Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 75% (8/12) subcutaneous tumors in one patient-derived xenograft (PDX) model harboring BRAF L597S that also harbored a BRAF variant of unknown significance, BRAF R239Q, however, was not sufficient to induce tumor shrinkage in a second PDX model with BRAF L597S, resulting only in tumor growth delay (PMID: 29903896). | 29903896 |
| NRAS Q61K NRAS mut | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |
| BRAF T470R | melanoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, Mekinist (trametinib) treatment resulted in an objective response rate of 33% (3/9, all partial responses) and a median progression-free survival (PFS) of 7.3 months in melanoma patients harboring BRAF fusions or non-V600 BRAF mutations, including a partial response with a tumor reduction of 87% and a PFS of 19.3 months in a patient harboring BRAF T470R (PMID: 33861486; NCT02296112). | 33861486 |
| MAP2K1 V60E | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 V60E in culture (PMID: 32641410). | 32641410 |
| MAP2K1 V60E | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 V60E in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 A76V | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A76V in culture (PMID: 36442478). | 36442478 |
| BRAF V487_P492delinsA | pancreatic carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
| NRAS G12D | multiple myeloma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a multiple myeloma cell line harboring NRAS G12D was sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 37339170). | 37339170 |
| MAP2K1 N109_R113del | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 N109_R113del in culture (PMID: 32641410). | 32641410 |
| BRAF K601E | pancreatic endocrine carcinoma | predicted - resistant | 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 Mekinist (trametinib) (PMID: 31158244). | 31158244 |
| MAP2K1 F53V | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F53V in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | colorectal cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). | 25309914 |
| BRAF V600E MAP2K1 L215F | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L215F in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 F53L | melanoma | conflicting | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 F53L | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek but not Erk phosphorylation and did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). | 36622773 |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 36442478). | 36442478 |
| MAP2K1 P105_I107delinsL | Advanced Solid Tumor | decreased response | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing MAP2K1 P105_I107delinsL were less sensitive to Mekinist (trametinib) compared to similar mutations in the negative regulatory domain of the Map2k1 protein in culture (PMID: 32641410). | 32641410 |
| BRAF G466V | lung adenocarcinoma | no benefit | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G466V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF V600E MAP2K1 Q58_E62del | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q58_E62del in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). | 24265153 |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S in culture (PMID: 36442478). | 36442478 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT01658553 | Phase I | Trametinib | A Study to Look at the Electrical Activity of the Heart in Subjects With Solid Tumor Cancers, Before and After Receiving the Study Treatment, GSK1120212 | Completed | USA | 0 |
| NCT01553851 | Phase II | Trametinib | GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer | Completed | USA | 0 |
| NCT02705963 | Phase I | Trametinib | A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors | Completed | USA | NLD | GBR | ESP | BEL | 0 |
| NCT02780128 | Phase I | Siremadlin Ceritinib + Ribociclib Trametinib | Next Generation Personalized Neuroblastoma Therapy | Terminated | USA | 0 |
| NCT02645149 | Phase II | Trametinib Pazopanib Ceritinib Ribociclib + Trametinib | Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (MatchMel) | Recruiting | AUS | 0 |
| NCT02015117 | Phase I | Trametinib | Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases | Active, not recruiting | USA | 0 |
| NCT06346067 | Phase III | LXH 254 + Trametinib Trametinib Dacarbazine Temozolomide | A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2) | Recruiting | USA | NLD | GBR | FRA | ESP | CZE | CAN | AUS | 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 |
| 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 |
| NCT01935973 | Phase II | Trametinib Trametinib + Uprosertib | Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer | Completed | USA | 0 |
| NCT03363217 | Phase Ib/II | Trametinib | Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway. | Active, not recruiting | CAN | 0 |
| NCT02042443 | Phase II | Fluorouracil + Leucovorin Capecitabine Trametinib | Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery | Completed | USA | 0 |
| NCT04801966 | Phase 0 | Palbociclib Alpelisib Atezolizumab Vemurafenib Ribociclib Talazoparib Cobimetinib Trametinib Abemaciclib Dabrafenib Nivolumab Binimetinib Pembrolizumab Encorafenib | Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (TAILOR) | Terminated | AUS | 0 |
| NCT02580708 | Phase Ib/II | Trametinib Rociletinib | A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) | Terminated | USA | 0 |
| NCT01725100 | Phase I | Trametinib | A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies | Completed | USA | 0 |
| NCT04417621 | Phase II | LTT462 + LXH 254 Trametinib Ribociclib | Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma | Active, not recruiting | USA | NOR | NLD | ITA | ISR | GBR | FRA | DEU | CHE | BEL | AUS | ARG | 0 |
| NCT04619316 | Phase II | Dabrafenib + Trametinib Trametinib | Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition (ERRITI) | Recruiting | DEU | 0 |
| NCT02881242 | Phase II | Trametinib | Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer | Active, not recruiting | USA | 0 |
| NCT02016729 | Phase I | Trametinib KRT-232 | A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia | Completed | 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 |
| 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 |
| NCT02152995 | Phase II | Trametinib | Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer | Active, not recruiting | USA | 0 |
| NCT02140840 | Phase II | Trametinib | A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib | Withdrawn | USA | 0 |
| NCT01376310 | Phase II | Docetaxel + Trametinib Erlotinib + Trametinib Trametinib Pemetrexed Disodium + Trametinib Carboplatin + Trametinib Nab-paclitaxel + Trametinib Gemcitabine + Trametinib Everolimus + Trametinib | GSK1120212 Rollover Study | Terminated | USA | NLD | FRA | CAN | 2 |
| NCT03878524 | Phase I | Oxaliplatin Palbociclib Vemurafenib Sirolimus Tretinoin Celecoxib Ipilimumab Ruxolitinib Dasatinib Abiraterone Idelalisib Trametinib Imatinib Erlotinib Carboplatin Olaparib Panobinostat Bortezomib Afatinib Fluorouracil Vorinostat Pembrolizumab Leucovorin Enzalutamide Ponatinib Nivolumab Everolimus Sunitinib Cabazitaxel Cabozantinib Lenvatinib Pertuzumab Sorafenib Venetoclax Bevacizumab | A Personalized Medicine Study for Patients With Advanced Cancer of the Breast, Prostate, Pancreas or Those With Refractory Acute Myelogenous Leukemia (SMMART) | Terminated | USA | 0 |
| NCT02296112 | Phase II | Trametinib | Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations | Completed | USA | 0 |
| NCT01231594 | Phase I | Dabrafenib Trametinib | A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors | Completed | USA | POL | ITA | GBR | FRA | ESP | DEU | CAN | AUS | 0 |
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| 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 |
| NCT03190915 | Phase II | Trametinib | Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia | Active, not recruiting | USA | 0 |
| NCT01467310 | Phase I | Trametinib | Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212 | Completed | USA | 0 |
| NCT01990196 | Phase II | Dasatinib Trametinib Degarelix + Enzalutamide | Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With/Without SRC or MEK Inhibition in Prostate Cancer | Active, not recruiting | USA | 0 |
| NCT03232892 | Phase II | Trametinib | Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer | Terminated | USA | 0 |
| NCT02070549 | Phase I | Trametinib | Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction | Active, not recruiting | USA | CAN | 0 |
| NCT03340506 | FDA approved | Trametinib Dabrafenib Dabrafenib + Trametinib | Dabrafenib and/or Trametinib Rollover Study | Recruiting | USA | NLD | HUN | FRA | ESP | DNK | DEU | AUT | ARG | 3 |
| NCT01979523 | Phase II | Trametinib Trametinib + Uprosertib | Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma | Completed | USA | GBR | FRA | 0 |
| 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 |
| NCT05180825 | Phase II | Vinblastine Trametinib | Pediatric Low Grade Glioma - MEKinhibitor TRIal vs Chemotherapy (PLGG - MEKTRIC) | Recruiting | FRA | 0 |
| NCT03148275 | Phase II | Trametinib | Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery | Completed | USA | 0 |
| NCT01827384 | Phase II | Adavosertib + Carboplatin Temozolomide + Veliparib Everolimus Trametinib | Molecular Profiling-Based Targeted Therapy in Treating Patients With Advanced Solid Tumors | Completed | USA | 0 |
| NCT02551718 | Phase I | Bosutinib Irinotecan Romidepsin Busulfan Melphalan Nilotinib Crizotinib Cytarabine Mitoxantrone Dasatinib Pazopanib Paclitaxel Clofarabine Hydroxyurea Tretinoin Carfilzomib Nelarabine Bexarotene Pentostatin Everolimus Cabozantinib Mercaptopurine Methotrexate Cladribine Thioguanine Daunorubicin Ponatinib Etoposide Afatinib Gefitinib Gemcitabine Regorafenib Arsenic trioxide Trametinib Imatinib Erlotinib Dabrafenib Decitabine Axitinib Azacitidine Ruxolitinib Fludarabine Lapatinib Ceritinib Sirolimus Sorafenib Lomustine Sunitinib Cabazitaxel Temsirolimus Topotecan Bortezomib Pralatrexate | High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia | Completed | USA | 0 |
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