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 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 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 |
| 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 |
| 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 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 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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