Molecular Profile Detail

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Profile Name BRAF D594N
Gene Variant Detail

BRAF D594N (loss of function - predicted)

Relevant Treatment Approaches MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor

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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