Therapy Detail
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| Therapy Name | LY3009120 + Trametinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| LY3009120 | DP-4978 | RAF Inhibitor (Pan) 27 | LY3009120 is a Pan-RAF inhibitor that inhibits signaling of all RAF isoforms and RAF dimers, which leads to inhibition of tumor cell growth (PMID: 26343583, PMID: 28576749). | |
| Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 24 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 |
|---|---|---|---|---|---|---|---|
| HRAS Q61K | rhabdomyosarcoma | sensitive | LY3009120 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture (PMID: 34737198). | 34737198 |
| NRAS Q61H | rhabdomyosarcoma | sensitive | LY3009120 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in a rhabdomyosarcoma cell line harboring NRAS Q61H in culture (PMID: 34737198). | 34737198 |
| NRAS Q61L | rhabdomyosarcoma | sensitive | LY3009120 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in a rhabdomyosarcoma cell line harboring NRAS Q61L in culture (PMID: 34737198). | 34737198 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | LY3009120 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated inhibition of Erk phosphorylation and greater inhibition of tumor growth when treated with the combination of Mekinist (trametinib) and LY3009120 compared to either agent alone (PMID: 34011980). | 34011980 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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