Molecular Profile Detail

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Profile Name BRAF L597Q
Gene Variant Detail

BRAF L597Q (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 L597Q Advanced Solid Tumor resistant 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 L597Q (PMID: 26343582). 26343582
BRAF L597Q lung cancer sensitive Ulixertinib Case Reports/Case Series Actionable In a Phase I trial, treatment with Ulixertinib (BVD-523) resulted in a partial response in a lung cancer patient harboring BRAF L597Q (PMID: 29247021; NCT01781429). 29247021
BRAF L597Q Advanced Solid Tumor resistant 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, 1 of the non-responding patients harbored BRAF L597Q (PMID: 29320312; NCT02091141). 29320312
BRAF L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, Koselugo (selumetinib) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q colon adenocarcinoma predicted - sensitive Sapitinib Preclinical - Patient cell culture Actionable In a preclinical study, Sapitinib (AZD8931) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) and Erbitux (cetuximab) synergistically inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial, Mekinist (trametinib) treatment resulted in an objective response rate of 33% (3/9, all partial responses) and a median progression-free survival (PFS) of 7.3 months in melanoma patients harboring BRAF fusions or non-V600 BRAF mutations, including a partial response with a tumor reduction of 38% and PFS ongoing 8.3 months in a patient harboring BRAF L597Q (PMID: 33861486; NCT02296112). 33861486
BRAF L597Q melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a retrospective analysis, first-line treatment with Mekinist (trametinib) resulted in a partial response lasting 6.2 months in a melanoma patient harboring BRAF L597Q, with 33% tumor shrinkage (PMID: 24933606). 24933606