Molecular Profile Detail

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Profile Name BRAF D594G
Gene Variant Detail

BRAF D594G (loss of function - predicted)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF D594G melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF D594G in culture (PMID: 28783719). 28783719
BRAF D594G gastrointestinal system cancer no benefit 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 progressive disease in 4 patients with gastrointestinal system cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
BRAF D594G prostate cancer no benefit 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 prostate cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
BRAF D594G lung adenocarcinoma no benefit 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 lung adenocarcinoma harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
BRAF D594G melanoma sensitive Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited Erk phosphorylation, reduced growth, and induced mitochondrial depolarization and apoptosis in melanoma cells harboring BRAF D594G in culture, and inhibited tumor growth and induced regression in a cell line xenograft model (PMID: 18794803). 18794803
BRAF D594G melanoma resistant U0126 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF D594G demonstrated resistance to U0126 treatment in culture (PMID: 18794803). 18794803
BRAF D594G lung adenocarcinoma no benefit Trametinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring BRAF D594G and TP53 H193L demonstrated stable disease for two months when treated with Mekinist (trametinib), but progressed after four months (PMID: 32540409). 32540409
BRAF D594G ampulla of Vater cancer predicted - sensitive Binimetinib + Encorafenib Case Reports/Case Series Actionable In a Phase II trial (BEAVER), combination treatment with Mektovi (binimetinib) and Braftovi (encorafenib) led to a confirmed partial response in an ampullary cancer patient harboring BRAF D594G, who remained on treatment for at least 5.4 months (Annals of Oncology 32 (2021): S596; NCT03839342). detail...
BRAF D594G melanoma predicted - sensitive Ulixertinib Case Reports/Case Series Actionable In a clinical case study, Ulixertinib (BVD-523) treatment resulted in a histologic response allowing for surgical resection in a patient with metastatic melanoma harboring BRAF D594G (PMID: 35551160; NCT04566393). 35551160
BRAF D594G colorectal cancer not predictive Cetuximab + Fluorouracil + Irinotecan + Leucovorin Case Reports/Case Series Actionable In a clinical study, the combination of Erbitux (cetuximab) with FOLFIRI resulted in one partial response with progression-free survival (PFS) of 3.2 months, and two with stable disease with PFS of 3.7 and 3.6 months in patients with metastatic colorectal cancer harboring BRAF D594G who had been previously treated with two lines of therapy (PMID: 31515458). 31515458
BRAF D594G colorectal cancer not predictive Fluorouracil + Irinotecan + Leucovorin + Panitumumab Case Reports/Case Series Actionable In a clinical study, the combination of Vectibix (panitumumab) with FOLFIRI as a third-line therapy resulted in stable disease with progression-free survival of 2.6 months in a patient with metastatic colorectal cancer harboring BRAF D594G (PMID: 31515458). 31515458
BRAF D594G colorectal cancer not predictive Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab Case Reports/Case Series Actionable In a clinical study, the combination of Vectibix (panitumumab) with FOLFOX as a first-line therapy resulted in two partial responses with progression-free survival of 8.3 and 2.8 months and stable disease with progression-free survival of 7.0 months in patients with metastatic colorectal cancer harboring BRAF D594G (PMID: 31515458). 31515458
BRAF D594G colorectal cancer not predictive Cetuximab + Irinotecan Case Reports/Case Series Actionable In a clinical study, the combination of Erbitux (cetuximab) with Camptosar (irinotecan) as a third-line therapy resulted in stable disease in two patients with metastatic colorectal cancer harboring BRAF D594G, with progression-free survival of 2.2 and 6.6 months (PMID: 31515458). 31515458
BRAF D594G 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 one patient with a partial response with 6.7 months progression-free survival (PFS) and two with stable disease with PFS of 1.8 and 2.3 months in patients with metastatic colorectal cancer harboring BRAF D594G (PMID: 31515458). 31515458
BRAF D594G melanoma sensitive SIJ777 Preclinical - Cell culture Actionable In a preclinical study, SIJ777 inhibited Mek, Erk, and Akt phosphorylation, proliferation, migration, and invasion, and induced apoptosis in a melanoma cell line harboring BRAF D594G in culture (PMID: 33917428). 33917428
BRAF D594G mucosal melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a clinical case study, Belvarafenib (HM95573) treatment resulted in a partial response ongoing at 8.5 months in a mucosal melanoma patient harboring BRAF D594G (PMID: 38470950). 38470950