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Gene | BRAF |
Variant | fusion |
Impact List | fusion |
Protein Effect | unknown |
Gene Variant Descriptions | BRAF fusion indicates a fusion of the BRAF gene, but the fusion partner is unknown. |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF rearrange BRAF fusion |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF fusion | pilocytic astrocytoma | not applicable | N/A | Guideline | Diagnostic | BRAF fusions aid in the diagnosis of pilocytic astrocytoma (NCCN.org). | detail... |
BRAF fusion | pilocytic astrocytoma | not applicable | N/A | Guideline | Prognostic | BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (NCCN.org). | detail... |
BRAF fusion | 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 progressive disease in a patient with prostate cancer harboring a BRAF fusion (PMID: 31924734; NCT02465060). | 31924734 |
BRAF fusion | pilocytic astrocytoma | sensitive | Selumetinib | Guideline | Actionable | Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring a BRAF fusion (NCCN.org). | detail... |
BRAF fusion | high grade glioma | predicted - sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a Phase II trial (APEC1621J), Ulixertinib (BVD-523) treatment resulted in a 6-month progression-free survival rate of 37% but no objective response in pediatric and young adult patients with advanced solid tumors harboring MAPK pathway activation, however, a patient with high grade glioma harboring a BRAF fusion achieved prolonged stable disease and remained on treatment for 15 cycles (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3009; NCT03698994). | detail... |
BRAF fusion | low grade glioma | predicted - sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a Phase II trial (APEC1621J), Ulixertinib (BVD-523) treatment resulted in a 6-month progression-free survival rate of 37% but no objective response in pediatric and young adult patients with advanced solid tumors harboring MAPK pathway activation, however, a patient with low grade glioma harboring a BRAF fusion achieved prolonged stable disease and remained on treatment for 7 cycles (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3009; NCT03698994). | detail... |
BRAF fusion | skin melanoma | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with BRAF fusions (NCCN.org). | detail... |
BRAF fusion | Advanced Solid Tumor | predicted - sensitive | DCC-3084 | Preclinical - Cell culture | Actionable | In a preclinical study, DCC-3084 inhibited downstream signaling and proliferation in cells expressing a BRAF fusion in culture (Cancer Res (2023) 83 (7_Supplement): 4045). | detail... |
BRAF fusion | Advanced Solid Tumor | predicted - sensitive | PLX8394 | Phase Ib/II | Actionable | In a Phase I/II trial, PLX8394 treatment resulted in stable disease in 46% of patients with advanced solid tumors harboring BRAF fusions and a complete response with a duration of response of at least 51.8 months in a patient with melanoma harboring AGK-BRAF (J Clin Oncol 41, 2023 (suppl 16; abstr 3006); NCT02428712). | detail... |
BRAF fusion | childhood low-grade glioma | sensitive | Tovorafenib | FDA approved | Actionable | In a Phase II trial (FIREFLY-1) that supported FDA approval, Ojemda (tovorafenib) was well tolerated and resulted in an overall response rate (ORR) per RAPNO criteria of 51% (39/76, 28 partial and 11 minor responses), clinical benefit rate (CBR) of 82% (62/76), and median duration of response of 13.8 mo in pediatric patients with low-grade glioma harboring BRAF fusions, rearrangements, or BRAF V600 mutations, with an ORR of 52% (33/64) in patients harboring BRAF fusions (PMID: 37978284; NCT04775485). | detail... 37978284 |
BRAF fusion | Advanced Solid Tumor | predicted - sensitive | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase I trial (HM-RAFI-103), Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy demonstrated preliminary activity in patients with advanced solid tumors harboring BRAF fusions, resulting in an objective response rate of 60% (9/15, all partial responses), a disease control rate of 93.3% (14/15), with a median progression-free survival of 13.7 months, and a median duration of response of 12 months (Ann Oncol 34 (2023): S465; NCT03284502). | detail... |
BRAF fusion | Erdheim-Chester disease | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Cotellic (cobimetinib) treatment resulted in a partial response with a tumor reduction of 67% in a patient with Erdheim-Chester disease harboring a BRAF fusion, with the patient remaining on treatment for at least 22 months (PMID: 38922339; NCT01775072). | 38922339 |
BRAF fusion | high grade glioma | predicted - sensitive | Selumetinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Koselugo (selumetinib) treatment resulted in a partial response with a tumor reduction of 52% in a patient with high grade neuroepithelial tumor harboring a BRAF fusion (PMID: 38922339; NCT01775072). | 38922339 |
BRAF fusion | Advanced Solid Tumor | predicted - sensitive | Binimetinib + Exarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with the combination of Exarafenib (KIN-2787) and Mektovi (binimetinib) demonstrated safety in patients with NRAS-mutant melanoma (n=39) or other advanced solid tumors driven by BRAF class I or II alterations (n=10 and n=3) and resulted in one confirmed and one unconfirmed partial response in patients harboring BRAF fusions (n=3) (Ann Oncol (2024) 35 (Suppl_2): S491-S492; NCT04913285). | detail... |