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 (dabrafinib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, and BRAF V600E-mutant anaplastic thyroid cancer (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 23 MEK1 Inhibitor 22 MEK2 Inhibitor 20 | 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 (dabrafinib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, BRAF V600E-mutant anaplastic thyroid cancer, and for adult and pediatric patients of 6 years or older with unresectable or metastatic solid tumors 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 |
|---|---|---|---|---|---|---|---|
| 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 V600E | thyroid gland 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 |
| 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 |
| 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 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 | 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 |
| 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 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 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 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 |
| 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 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 |
| 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 |
| 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 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 |
| 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 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 |
| 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 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 |
| 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 | 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 |
| 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 |
| 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 |
| 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 |
| 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 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 |
| FGFR2 - TACC3 FGFR2 V565F | intrahepatic cholangiocarcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment reduced viability of cells derived from a TP53-null intrahepatic cholangiocarcinoma mouse model expressing FGFR2 V565F in the context of FGFR2-TACC3 fusion in culture (PMID: 33741397). | 33741397 |
| 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 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 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 |
| 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 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 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 |
| 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 |
| 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 |
| 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 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 |
| FGFR2 - TACC3 | intrahepatic cholangiocarcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment inhibited growth and viability of cells derived from a TP53-null intrahepatic cholangiocarcinoma mouse model expressing FGFR2-TACC3 fusion in tumoroid and 2D cell culture (PMID: 33741397). | 33741397 |
| 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 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 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 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 |
| 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 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 | 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 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 |
| 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 |
| 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 |
| 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 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 |
| 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 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 |
| 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 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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 |
| 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 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 C121S | melanoma | resistant | 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 | resistant | 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 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 P162S | melanoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 |
| 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 |
| 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 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 |
| 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 |
| 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 N486_P490del | pancreatic ductal adenocarcinoma | predicted - 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 | predicted - 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 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 |
| 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 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| BRAF mutant | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF 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/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 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 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 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 |
| 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 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 |
| 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 | 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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... |
| 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 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 |
| 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 L485_P490delinsY | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to Mekinist (trametinib), resulting in cell growth inhibition (PMID: 26732095). | 26732095 |
| 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 |
| 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 |
| 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 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, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| 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 |
| 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 N486_P490del | ovarian cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). | 26732095 |
| 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 |
| KMT2A - MLLT3 NRAS G12D | leukemia | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of NRAS G12D in murine leukemia cells harboring KMT2A-MLLT3 resulted in increased sensitivity to treatment with Mekinist (trametinib) in culture (PMID: 33563661). | 33563661 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| FGFR2 - CCDC6 | intrahepatic cholangiocarcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment reduced growth of tumoroids derived from a TP53-null intrahepatic cholangiocarcinoma mouse model expressing FGFR2-CCDC6 fusion in culture (PMID: 33741397). | 33741397 |
| 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 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 V504_R506dup | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Mekinist (trametinib) in culture (PMID: 30575814). | 30575814 |
| FGFR2 - BICC1 | intrahepatic cholangiocarcinoma | no benefit | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) treatment inhibited growth and viability of cells derived from a TP53-null intrahepatic cholangiocarcinoma mouse model expressing FGFR2-BICC1 fusion in tumoroid and 2D cell culture, but demonstrated only marginal growth inhibition in a subcutaneous allograft mouse model (PMID: 33741397). | 33741397 |
| 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 | 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 |
| 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 |
| 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 |
| 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 |
| 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 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 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 |
| 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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 |
| BRAF V600E PDGFRB over exp | melanoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and overexpressing Pdgfrb demonstrated resistance to Mekinist (trametinib) in culture (PMID: 28986383). | 28986383 |
| 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 |
| 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 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT03784014 | Phase III | Ceritinib Dabrafenib + Trametinib Capmatinib Durvalumab + Olaparib Nilotinib Futibatinib Trametinib Palbociclib Glasdegib Lapatinib | Molecular Profiling of Advanced Soft-tissue Sarcomas (MULTISARC) | Recruiting | FRA | 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 | ITA | FRA | DEU | BEL | AUT | 7 |
| NCT01467310 | Phase I | Trametinib | Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212 | 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 |
| NCT03190915 | Phase II | Trametinib | Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia | Recruiting | USA | 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 |
| NCT01979523 | Phase II | Trametinib Trametinib + Uprosertib | Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma | Completed | USA | FRA | 1 |
| 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 |
| NCT05182931 | Phase II | Dabrafenib + Trametinib Trametinib | A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study) | Recruiting | 1 | |
| NCT02780128 | Phase I | Siremadlin Ceritinib + Ribociclib Trametinib | Next Generation Personalized Neuroblastoma Therapy | Recruiting | USA | 0 |
| NCT02152995 | Phase II | Trametinib | Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer | Active, not recruiting | USA | 0 |
| NCT02296112 | Phase II | Trametinib | Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations | Completed | 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 |
| NCT02070549 | Phase I | Trametinib | Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction | Active, not recruiting | USA | CAN | 0 |
| NCT05180825 | Phase II | Vinblastine Trametinib | Pediatric Low Grade Glioma - MEKinhibitor TRIal vs Chemotherapy (PLGG - MEKTRIC) | Recruiting | FRA | 0 |
| NCT01231594 | Phase I | Dabrafenib Trametinib | A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors | Completed | USA | ITA | FRA | ESP | DEU | CAN | 3 |
| 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) | 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 |
| NCT02881242 | Phase II | Trametinib | Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer | Active, not recruiting | USA | 0 |
| NCT01935973 | Phase II | Trametinib Trametinib + Uprosertib | Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer | Completed | USA | 0 |
| NCT03232892 | Phase II | Trametinib | Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer | Terminated | USA | 0 |
| NCT04619316 | Phase II | Dabrafenib + Trametinib Trametinib | Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition (ERRITI) | Recruiting | DEU | 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 | FRA | CAN | 3 |
| 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) | Active, not recruiting | FRA | 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 |
| 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 |
| 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) | Recruiting | 1 | |
| NCT02015117 | Phase I | Trametinib | Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases | Active, not recruiting | USA | 0 |
| NCT02101788 | Phase II | Topotecan Letrozole + Paclitaxel + Pegylated liposomal-doxorubicin + Tamoxifen Trametinib | Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer | Active, not recruiting | USA | 1 |
| 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 |
| 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 |
| NCT03363217 | Phase Ib/II | Trametinib | Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway. | Recruiting | CAN | 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 | ESP | BEL | 2 |
| 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 | FRA | CAN | 2 |
| NCT03340506 | FDA approved | Trametinib Dabrafenib Dabrafenib + Trametinib | Dabrafenib and/or Trametinib Rollover Study | Recruiting | USA | FRA | ESP | DEU | AUT | 7 |
| NCT03148275 | Phase II | Trametinib | Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
| NCT01553851 | Phase II | Trametinib | GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer | Completed | USA | 0 |
| NCT02465060 | Phase II | Erdafitinib Trametinib Crizotinib Sapanisertib AZD4547 Dasatinib Osimertinib Palbociclib Capivasertib Larotrectinib Ulixertinib Nivolumab + Relatlimab Copanlisib Sunitinib Nivolumab Pertuzumab + Trastuzumab Ipatasertib Dabrafenib + Trametinib Binimetinib Adavosertib Afatinib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Taselisib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Recruiting | USA | 2 |
| 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 |
| NCT02645149 | Phase II | Trametinib Pazopanib Ceritinib Ribociclib + Trametinib | Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (MatchMel) | Recruiting | 1 |
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