Molecular Profile Detail

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Profile Name BRAF T599dup
Gene Variant Detail

BRAF T599dup (gain of function)

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 T599dup melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in regression of lymphadenopathy, lung nodules, and subcutaneous nodules in a patient with metastatic melanoma harboring BRAF T599dup, and at 9 months from treatment initiation, a partial response was still observed (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical study, a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in partial responses in 4 patients with metastatic melanoma harboring BRAF T599dup, with one patient also harboring CTNNB1 I35T (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) resulted in disease progression in two patients with metastatic melanoma harboring BRAF T599dup (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination resulted in partial metabolic remission within six weeks in a patient with metastatic melanoma harboring BRAF T599dup (PMID: 29494756). 29494756
BRAF T599dup lung adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring BRAF T599dup demonstrated a response to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), with regression of the left lower lobe bronchial tumor (PMID: 33704186). 33704186
BRAF T599dup colorectal cancer predicted - resistant 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 progressive disease in a patient with metastatic colorectal cancer harboring BRAF T599dup (PMID: 31515458). 31515458
BRAF T599dup colorectal cancer resistant Cetuximab Preclinical - Pdx Actionable In preclinical study, a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF T599dup was resistant to Erbitux (cetuximab) treatment (PMID: 31515458). 31515458
BRAF T599dup ganglioglioma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in clinical improvement and tumor shrinkage with ongoing stable disease for at least 15 months in a pediatric patient with ganglioglioma harboring BRAF T599dup (PMID: 33637608). 33637608
BRAF T599dup Advanced Solid Tumor sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited downstream signaling and viability in transformed cells expressing BRAF T599dup in culture (PMID: 38662982). 38662982
BRAF T599dup Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited downstream signaling and viability in transformed cells expressing BRAF T599dup in culture (PMID: 38662982). 38662982
BRAF T599dup lung adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in 12.3% tumor shrinkage in a patient with lung adenocarcinoma harboring BRAF T599dup along with KRAS Q61H, however, treatment was discontinued for adverse events (PMID: 38662982). 38662982