Molecular Profile Detail

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Profile Name BRAF K601E
Gene Variant Detail

BRAF K601E (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 K601E Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). 22798288
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601E (PMID: 26343582). 26343582
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). 28344857
BRAF K601E melanoma no benefit Dabrafenib Phase I Actionable In a Phase I trial, no responses were demonstrated among three melanoma patients with non-V600 BRAF mutations, including two patients harboring BRAF K601E, following treatment with Tafinlar (dabrafenib), compared to a confirmed response rate of 50% in patients harboring BRAF V600 mutations (PMID: 22608338). 22608338
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). 23248257
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 6 of the non-responding patients harbored BRAF K601E (PMID: 29320312; NCT02091141). 29320312
BRAF K601E pancreatic endocrine carcinoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 31158244). 31158244
BRAF K601E pancreatic endocrine carcinoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 31158244). 31158244
BRAF K601E lung non-small cell carcinoma no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF K601E, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF K601E prostate adenocarcinoma 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 a near partial response in a patient with prostate adenocarcinoma harboring BRAF K601E until disease progression at 9.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF K601E melanoma predicted - sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment induced limited apoptosis and inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). 18794803
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor U0126 Preclinical - Cell culture Actionable In a preclinical study, U0126 treatment inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). 18794803
BRAF K601E colorectal cancer predicted - sensitive PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment resulted in partial inhibition of tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E colorectal cancer resistant Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E colorectal cancer resistant Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment in combination with Zelboraf (vemurafenib) did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E colorectal cancer sensitive Cetuximab + PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E lung adenocarcinoma 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 therapy resulted in a partial response lasting at least nine months with near-complete tumor regression in a patient with lung adenocarcinoma harboring BRAF K601E (PMID: 34590045). 34590045
BRAF K601E 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) treatment resulted in a partial response in a patient with metastatic melanoma harboring BRAF K601E, increased inhibition of Erk1/2 phosphorylation in a melanoma cell line expressing BRAF K601E in culture, and increased tumor growth inhibition in a patient-derived xenograft (PDX) model compared to Mekinist (trametinib) alone (PMID: 30248172). 30248172
BRAF K601E melanoma no benefit Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in transient disease stabilization followed by metastatic progression in a patient with metastatic melanoma harboring BRAF K601E (PMID: 31182949). 31182949
BRAF K601E papillary thyroid carcinoma predicted - sensitive Denosumab + Sorafenib Case Reports/Case Series Actionable In a clinical case study, Nexavar (sorafenib) and Xgeva (denosumab) treatment resulted in stable bone disease and complete responses in the lung and lymph node metastases in a patient with papillary thyroid carcinoma harboring BRAF K601E (PMID: 35630083). 35630083
BRAF K601E colorectal cancer resistant Cetuximab Preclinical - Pdx Actionable In preclinical study, a colorectal patient-derived xenograft (PDX) model harboring BRAF K601E was resistant to Erbitux (cetuximab) treatment (PMID: 31515458). 31515458
BRAF K601E colorectal cancer predicted - resistant Panitumumab Case Reports/Case Series Actionable In a clinical study, Vectibix (panitumumab) treatment as a third-line therapy resulted in progressive disease in a metastatic colorectal cancer patient harboring BRAF K601E (PMID: 31515458). 31515458
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a retrospective analysis, treatment with Mekinist (trametinib) resulted in a clinical benefit rate of 75% (3/4) in melanoma patients harboring BRAF K601E, with two partial responses each lasting 2.5 and 5.5 months, and one with stable disease lasting 3.6 months with a 27% reduction in tumor mass (PMID: 24933606). 24933606
BRAF K601E Advanced Solid Tumor sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation of a cell line expressing BRAF K601E in culture (PMID: 37164118). 37164118
BRAF K601E melanoma sensitive PF-07799933 Preclinical - Pdx Actionable In a preclinical study, PF-07799933 treatment resulted in tumor regression in a patient-derived xenograft (PDX) model of melanoma harboring BRAF K601E (PMID: 38691346). 38691346
BRAF K601E colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Cetuximab + Encorafenib Case Reports/Case Series Actionable In a clinical case study, third-line treatment with the combination of Mektovi (binimetinib), Erbitux (cetuximab), and Braftovi (encorafenib) resulted in improvement in the pleural effusion and ascites in a patient with metastatic colon adenocarcinoma harboring BRAF K601E, however, progression occurred after 2 months of treatment (PMID: 39072179). 39072179