Molecular Profile Detail

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Profile Name BRAF G466V
Gene Variant Detail

BRAF G466V (loss 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 G466V lung non-small cell carcinoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung cancer cells expressing BRAF G466V in culture (PMID: 22649091). 22649091
BRAF G466V lung non-small cell carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring BRAF G466V mutation in culture (PMID: 26090892). 26090892
BRAF G466V lung non-small cell carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 27523909). 27523909
BRAF G466V lung non-small cell carcinoma no benefit Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring BRAF G466V demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466V lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). 28783719
BRAF G466V colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer predicted - resistant Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit ERK signaling or tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer not predictive Irinotecan + Panitumumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan) (PMID: 28783719). 28783719
BRAF G466V lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 28947956). 28947956
BRAF G466V lung adenocarcinoma sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G466V in culture (PMID: 27834212). 27834212
BRAF G466V lung cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of lung cancer cells harboring BRAF G466V in culture (PMID: 30104724). 30104724
BRAF G466V Advanced Solid Tumor no benefit 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 G466V (PMID: 29320312; NCT02091141). 29320312
BRAF G466V 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 G466V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G466V Advanced Solid Tumor 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 progressive disease in a patient with tumor of unknown primary harboring BRAF G466V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V lung 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 progressive disease in a patient with lung adenocarcinoma harboring BRAF G466V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V lung cancer predicted - sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring BRAF G466V demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). 30559419
BRAF G466V colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V colorectal cancer resistant PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V colorectal cancer predicted - resistant Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V colorectal cancer sensitive Cetuximab + PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V colorectal cancer sensitive Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V lung cancer predicted - sensitive CFT1946 Preclinical - Cell culture Actionable In a preclinical study, CFT1946 treatment inhibited proliferation of a lung cancer cell line harboring heterozygous BRAF G466V in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 2158). detail...
BRAF G466V 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 a partial response with 6.1 months progression-free survival in a patient with metastatic colorectal cancer harboring BRAF G466V (PMID: 31515458). 31515458
BRAF G466V lung non-small cell carcinoma sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 37164118). 37164118
BRAF G466V lung non-small cell carcinoma sensitive SIJ777 Preclinical - Cell culture Actionable In a preclinical study, SIJ777 inhibited proliferation of a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 33917428). 33917428
BRAF G466V lung adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, first-line treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response after 3 months in a patient with metastatic lung adenocarcinoma harboring BRAF G466V (PMID: 38283732). 38283732
BRAF G466V lung non-small cell carcinoma predicted - sensitive PF-07799933 Preclinical - Biochemical Actionable In a preclinical study, PF-07799933 inhibited Erk phosphorylation in non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 38691346). 38691346