OKI-179 + binimetinib

OKI-179 + binimetinib is an investigational combination therapy being studied primarily for the treatment of advanced NRAS-mutated melanoma and other solid tumors with RAS pathway mutations. OKI-179 (also known as bocodepsin) is a novel, orally bioavailable, Class I-selective histone deacetylase (HDAC) inhibitor that acts by inhibiting Class I HDACs (1, 2, 3, and 8), leading to changes in gene expression that can suppress tumor growth. It is a prodrug metabolized to the active largazole derivative OKI-006. Binimetinib is a small molecule MEK inhibitor targeting MEK1 and MEK2 within the MAPK/ERK signaling pathway. The combination leverages synthetic lethality between HDAC inhibition and MAPK pathway blockade to enhance anti-tumor activity in RAS-mutant cancers. This regimen has shown promising preclinical synergy and tolerability profiles[3][4][5][7].