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Gene | BRAF |
Variant | class 2 |
Impact List | unknown |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF Class 2 variants are BRAF variants that activate BRAF and downstream signaling in a dimer-dependent, RAS-independent manner (PMID: 28783719, PMID: 26343582). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF class 2 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF class 2 | colorectal cancer | decreased response | Cetuximab | Clinical Study | Actionable | In a clinical study, colorectal cancer patients harboring class 2 BRAF mutations demonstrated a decreased response to treatment with the combination of either Erbitux (cetuximab) or Vectibix (panitumumab) plus chemotherapy compared to those with class 3 BRAF mutations, with a response rate of 8% (1/12) vs 50% (14/28) (P=0.02), respectively, in first, second, third or later-line setting and a response rate of 17% (1/6) vs 78% (7/9) (P=0.04), respectively, in the first or second-line setting (PMID: 31515458). | 31515458 |
BRAF class 2 | colorectal cancer | decreased response | Panitumumab | Clinical Study | Actionable | In a clinical study, colorectal cancer patients harboring class 2 BRAF mutations demonstrated a decreased response to treatment with the combination of either Erbitux (cetuximab) or Vectibix (panitumumab) plus chemotherapy compared to those with class 3 BRAF mutations, with a response rate of 8% (1/12) vs 50% (14/28) (P=0.02), respectively, in first, second, third or later-line setting and a response rate of 17% (1/6) vs 78% (7/9) (P=0.04), respectively, in the first or second-line setting (PMID: 31515458). | 31515458 |
BRAF class 2 | Advanced Solid Tumor | no benefit | Belvarafenib | Phase II | Actionable | In a Phase II trial (TAPISTRY), Belvarafenib (HM95573) treatment did not result in any confirmed objective responses in patients with advanced solid tumors harboring BRAF class II alterations (including mutations, fusion positive, or intragenic deletions), with a clinical benefit rate of 3.8% (1/26), 42.3% (11/26) with stable disease, a median progression-free survival of 2.1 months, and a median overall survival of 4.8 months (Ann Oncol (2024) 35 (Suppl_2): S498-S499; NCT04589845). | detail... |
BRAF class 2 | pancreatic cancer | predicted - sensitive | Exarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Exarafenib (KIN-2787) treatment led to inhibition of tumor growth in a pancreatic cell line xenograft model harboring a BRAF class 2 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). | detail... |
BRAF class 2 | Advanced Solid Tumor | predicted - sensitive | Exarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Exarafenib (KIN-2787) was tolerated and resulted in a partial response in 17.6% (6/34) and stable disease in 23.5% (8/34) of patients with BRAF-driven advanced solid tumors or NRAS-driven melanoma, including a partial response in 1 patient harboring a BRAF class 2 mutation (Cancer Res (2023) 83 (8_Supplement): CT032; NCT04913285). | detail... |
BRAF class 2 | Advanced Solid Tumor | predicted - sensitive | BDTX-4933 | Preclinical - Cell culture | Actionable | In a preclinical study, BDTX-4933 inhibited proliferation of cells expressing a BRAF class 2 mutation in culture (Eur J Cancer (2022), Vol 174, Supplement 1: S86). | detail... |
BRAF class 2 | 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 class 2 mutation in culture (Cancer Res (2023) 83 (7_Supplement): 4045). | detail... |