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Profile Name | BRAF D594N |
Gene Variant Detail | |
Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
BRAF D594N | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Mek in transformed cells expressing BRAF D594N in culture (PMID: 28783719). | 28783719 | |
BRAF D594N | lung non-small cell carcinoma | predicted - sensitive | RMC-4550 | Preclinical - Pdx | Actionable | In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF D594N (PMID: 30104724). | 30104724 | |
BRAF D594N | female reproductive organ cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecological cancer harboring BRAF D594N (PMID: 31924734; NCT02465060). | 31924734 |
BRAF D594N | colorectal cancer | not predictive | Irinotecan + Panitumumab | Case Reports/Case Series | Actionable | In a clinical study, the combination of Vectibix (panitumumab) with Camptosar (irinotecan) as a third-line therapy resulted in partial responses with 14.9 and 14.7 months progression-free survival in two patients with metastatic colorectal cancer harboring BRAF D594N (PMID: 31515458). | 31515458 | |
BRAF D594N | colorectal cancer | not predictive | Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Erbitux (cetuximab) treatment inhibited tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF D594N (PMID: 31515458). | 31515458 | |
BRAF D594N | gallbladder cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a Phase II trial (BEAVER), combination treatment with Mektovi (binimetinib) and Braftovi (encorafenib) led to stable disease in a gallbladder cancer patient harboring BRAF D594N, with a treatment duration of 4.4 months (Annals of Oncology 32 (2021): S596; NCT03839342). | detail... |
BRAF D594N | lung adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) | NST-628 | Preclinical - Pdx | Actionable | In a preclinical study, NST-628 treatment resulted in an overall response rate of 69.5% in a panel of patient-derived xenograft (PDX) models of solid tumors harboring RAS-MAPK pathway alterations, including 1 response out of 2 lung adenocarcinoma patient-derived xenograft (PDX) models harboring BRAF D594N (PMID: 38588399). | 38588399 |