Combination of the Novel RAF Dimer Inhibitor Brimarafenib With the MEK Inhibitor Mirdametinib Is Effective Against NRAS Mutant Melanoma.

ABSTRACT: Metastatic melanoma, the most aggressive form of skin cancer, accounts for the majority of skin cancer-related deaths. While targeted kinase inhibitors have improved outcomes for patients with BRAF-mutated melanomas, their efficacy is often short-lived, and effective treatments for other mutations, such as NRAS, remain scarce. To address this clinical need, we investigated the combination of the novel panRAF inhibitor, brimarafenib, and the MEK inhibitor, mirdametinib, both of which target the MAPK pathway downstream of NRAS. This study demonstrates the efficacy of this combination in NRAS-mutated melanoma and is currently also investigated in a phase I/IIa clinical study. In vitro, the brimarafenib and mirdametinib combination exhibited synergistic effects, significantly inhibiting the gr

SUBMITTER: Tellenbach FL 

PROVIDER: S-EPMC12592225 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature