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Ref Type Journal Article
PMID (38470950)
Authors Kim KH, Cho S, Jeong Y, Baek ES, Lee C, Ryu HJ, Noh YS, Hong YH, Chung KY, Roh MR, Oh BH, Kim CG, Jung M, Shin SJ
Title Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma.
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Abstract Text Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP).Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib.Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses.Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61L mucosal melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a clinical case study, Belvarafenib (HM95573) treatment resulted in a partial response with a progression-free survival of 6.2 months in a mucosal melanoma patient harboring NRAS Q61L (PMID: 38470950). 38470950
BRAF D594G mucosal melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a clinical case study, Belvarafenib (HM95573) treatment resulted in a partial response ongoing at 8.5 months in a mucosal melanoma patient harboring BRAF D594G (PMID: 38470950). 38470950
NRAS G12A melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a clinical case study, Belvarafenib (HM95573) treatment resulted in a partial response with a progression-free survival of 4.2 months in a melanoma patient harboring NRAS G12A (PMID: 38470950). 38470950