Therapy Detail
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| Therapy Name | Navitoclax + Trametinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Navitoclax | ABT-263 | BCL-XL inhibitor 14 BCL2 inhibitor 27 | Navitoclax (ABT-263) is a BCL2, BCL-XL, and BCL-W inhibitor, which may enhance the efficacy of chemotherapeutics (PMID: 25787766, PMID: 32513939). | |
| 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). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E | lung non-small cell carcinoma | sensitive | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| NRAS act mut | neuroblastoma | predicted - sensitive | Navitoclax + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an NRAS activating mutation to Navitoclax (ABT-263), resulting in reduced cell viability in culture, and the combination treatment resulted in tumor regression in cell line xenograft models (6/6 partial responses) (PMID: 36895472). | 36895472 |
| NRAS Q61R | ovarian cancer | predicted - sensitive | Navitoclax + Trametinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, treatment with the combination of Navitoclax (ABT-263) and Mekinist (trametinib) resulted in a partial response rate of 33.3% (7/21) amongst efficacy evaluable patients with gynecologic cancers harboring mutations in KRAS or NRAS, including a partial response in a patient with ovarian cancer harboring NRAS Q61R (PMID: 38456660; NCT02079740). | 38456660 |
| BRAF V600E | melanoma | sensitive | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| ALK act mut | neuroblastoma | predicted - sensitive | Navitoclax + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Mekinist (trametinib) sensitized neuroblastoma cell lines harboring ALK activating mutations to Navitoclax (ABT-263), resulting in reduced cell viability in culture (PMID: 36895472). | 36895472 |
| NRAS mutant | female reproductive organ cancer | sensitive | Navitoclax + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the combination of Navitoclax (ABT-263) and Mekinist (trametinib) resulted in a partial response rate of 33.3% (7/21) amongst efficacy evaluable patients with gynecologic cancers harboring mutations in KRAS or NRAS, with a median duration of response of 8.17 months, a median progression-free survival of 4.8 months, and a median overall survival of 18.13 months (PMID: 38456660; NCT02079740). | 38456660 |
| BRAF V600E | colon cancer | sensitive | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02079740 | Phase Ib/II | Navitoclax + Trametinib | Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors | Active, not recruiting | USA | 0 |
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