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Therapy Name | Dacarbazine + Selumetinib |
Synonyms | |
Therapy Description | |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Dacarbazine | Deticene | Biocarbazine R | Chemotherapy - Alkylating 14 | Deticene (dacarbazine) alkylates and cross-links DNA, which disrupts the cell-cycle. Dacarbazine is FDA approved for melanoma (FDA.gov). |
Selumetinib | Koselugo | AZD6244|ARRY-142886 | MEK inhibitor (Pan) 22 MEK1 Inhibitor 20 MEK2 Inhibitor 18 | Koselugo (selumetinib) inhibits mitogen-activated protein kinase kinases (MEK or MAPK/ERK kinases) 1 and 2, which may prevent the activation of MEK1/2-dependent effector proteins and transcription factors, reducing cellular proliferation in various cancers (PMID: 27467210). Koselugo (selumetinib) is FDA approved for use in pediatric patients of 2 years or older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
Unknown unknown | Advanced Solid Tumor | not applicable | Dacarbazine + Selumetinib | Phase I | Actionable | In a Phase I trial, the combination of Koselugo (selumetinib) and Deticene (dacarbazine) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with partial responses in 17% (4/23) and stable disease for greater than 6 weeks in 65% (15/23) of patients (PMID: 28264648). | 28264648 |
GNAQ mutant | uveal melanoma | no benefit | Dacarbazine + Selumetinib | Phase III | Actionable | In a Phase III trial (SUMIT), Koselugo (selumetinib) in combination with Deticene (dacarbazine) did not significantly improve progression-free survival (2.8 vs 1.8 months, HR=0.78, p=0.32) or overall survival (HR=0.75, p=0.40) in patients with metastatic uveal melanoma, 94% (73/78) of analyzed patients harbored mutually exclusive GNAQ or GNA11 mutations (PMID: 29528792; NCT01974752). | 29528792 |
GNA11 mutant | uveal melanoma | no benefit | Dacarbazine + Selumetinib | Phase III | Actionable | In a Phase III trial (SUMIT), Koselugo (selumetinib) in combination with Deticene (dacarbazine) did not significantly improve progression-free survival (2.8 vs 1.8 months, HR=0.78, p=0.32) or overall survival (HR=0.75, p=0.40) in patients with metastatic uveal melanoma, 94% (73/78) of analyzed patients harbored mutually exclusive GNAQ or GNA11 mutations (PMID: 29528792; NCT01974752). | 29528792 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT01974752 | Phase III | Dacarbazine + Selumetinib | Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) | Completed | USA | CAN | 9 |