plixorafenib + cobicistat

A combination of **plixorafenib** (FORE8394, PLX8394), a novel orally available next-generation small-molecule selective inhibitor of BRAF alterations (“paradox breaker” RAF inhibitor), and **cobicistat**, a potent cytochrome P450 3A (CYP3A) inhibitor and pharmacokinetic enhancer. Plixorafenib is designed to target both V600 and non-V600 BRAF mutations and fusions, including those frequently found in advanced solid and central nervous system (CNS) tumors. Cobicistat is co-administered to increase plixorafenib exposure by inhibiting its metabolic clearance. The combination is under clinical development for patients with BRAF-altered malignancies, especially BRAF V600E-mutant and fusion-positive CNS tumors and advanced solid tumors, including thyroid cancer, glioma, and melanoma. Plixorafenib + cobicistat is not approved and is administered orally in ongoing phase 2 trials[1][2][3][4][5][6][7][8].