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Therapy Name | Milademetan + Trametinib |
Synonyms | |
Therapy Description | |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Milademetan | DS-3032b|Milademetan Tosylate|DS3032b|DS 3032b|RAIN-32 | MDM2 Inhibitor 23 | Milademetan binds to MDM2 and prevents binding to p53, resulting in activation of p53 signaling and increased tumor cell apoptosis (PMID: 29416773, PMID: 32651541). | |
Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | Mekinist (trametinib) inhibits MEK 1 and 2, which potentially leads to reduced tumor cell proliferation (PMID: 27956260). Mekinist (trametinib) is FDA approved for melanoma patients harboring BRAF V600E or BRAF V600K mutations, and in combination with Tafinlar (dabrafenib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, BRAF V600E-mutant anaplastic thyroid cancer, for adult and pediatric patients of 6 years or older with unresectable or metastatic solid tumors harboring BRAF V600E, and for pediatric patients of 1 year or older with low-grade glioma harboring BRAF V600E (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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BRAF G469A MDM2 amp TP53 wild-type | lung adenocarcinoma | sensitive | Milademetan + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Milademetan synergistically inhibited proliferation in a lung adenocarcinoma cell line harboring BRAF G469A with wild-type TP53 and MDM2 amplification in culture (PMID: 37182602). | 37182602 |
EML4 - ALK MDM2 amp TP53 wild-type | lung adenocarcinoma | sensitive | Milademetan + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Milademetan resulted in increased tumor growth inhibition compared to either therapy alone in a patient-derived xenograft model of lung adenocarcinoma harboring wild-type TP53, EML4-ALK, and MDM2 amplification (PMID: 37182602). | 37182602 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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