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Profile Name | BRAF fusion |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | 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 | low grade glioma | predicted - sensitive | Tovorafenib | Phase II | Actionable | In a Phase II trial (FIREFLY-1), Tovorafenib (MLN2480) therapy was well tolerated and led to an overall response rate of 67% (46/69, 12 complete and 34 partial responses), clinical benefit rate (CBR) of 93% (64/69), median progression-free survival of 19.4 mo, and median duration of response of 16.6 mo in pediatric patients with low-grade glioma harboring BRAF fusions (n=59) or BRAF V600E (n=10), with an ORR of 69% (41/59) and CBR of 93% (55/59) in patients with a BRAF fusion (PMID: 37978284; NCT04775485). | 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... |