fexofenadine + osimertinib

Fexofenadine + osimertinib is an investigational drug combination consisting of fexofenadine, a second-generation antihistamine and P-glycoprotein substrate, and osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Osimertinib is approved for the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Recent research has identified that fexofenadine may act as a MET inhibitor and can counteract resistance to osimertinib in NSCLC driven by MET amplification—a common mechanism of acquired resistance to EGFR-targeted therapies. Preclinical studies show that this combination restores drug sensitivity and enhances antitumor efficacy more robustly than either agent alone in models of MET-amplified or EGFR T790M-mutated NSCLC. Pharmacokinetic studies indicate that coadministration increases exposure to fexofenadine due to weak inhibition of P-glycoprotein by osimertinib[1][2][4].