Therapy Detail

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Therapy Name Ganitumab + Trametinib
Synonyms
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Ganitumab AMG-479 IGF-1R Inhibitor 17 Ganitumab (AMG-479) is a recombinant antibody that binds to and inhibits IGF-1R. Inhibition of IGF-1R prevents activation of the downstream PI3K/Akt pathway, which may inhibit proliferation and induce apoptosis of tumor cells (NCI Drug Dictionary).
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
NRAS Q61H PTEN over exp rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Ganitumab (AMG-479) sensitized a rhabdomyosarcoma cell line harboring NRAS Q61H and overexpressing PTEN to treatment with Mekinist (trametinib), resulting in reduced cell growth in culture (PMID: 36322002). 36322002
NRAS G13D rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring NRAS G13D (PMID: 36322002). 36322002
NRAS G13R PIK3CA H1047R rhabdomyosarcoma resistant Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring NRAS G13R and PIK3CA H1047R was resistant to the Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment (PMID: 36322002). 36322002
HRAS Q61K PTEN dec exp rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Ganitumab (AMG-479) sensitized a rhabdomyosarcoma cell line harboring HRAS Q61K with low PTEN expression to treatment with Mekinist (trametinib), resulting in reduced cell growth in culture (PMID: 36322002). 36322002
NRAS Q61H rhabdomyosarcoma predicted - sensitive Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of a rhabdomyosarcoma cell line harboring NRAS Q61H in culture, but did not improve tumor suppression and survival compared to monotherapy in a cell line xenograft model (PMID: 36322002). 36322002
HRAS Q61K rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, and resulted in tumor regression and increased survival compared to either treatment alone in a cell line xenograft model (PMID: 36322002). 36322002
HRAS G13R rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring HRAS G13R (PMID: 36322002). 36322002

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries


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