osimertinib + trametinib

Osimertinib + trametinib is an investigational combination therapy consisting of two small molecule inhibitors used in the treatment of non-small cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine kinase inhibitors. Osimertinib is a third-generation irreversible inhibitor of the epidermal growth factor receptor (EGFR) that selectively targets both sensitizing and T790M resistance mutations while sparing wild-type EGFR. Trametinib is a reversible allosteric inhibitor of MEK1 and MEK2 kinases in the MAPK pathway. The rationale for combining these agents arises from preclinical and clinical evidence that activation of downstream MAPK signaling (via BRAF or KRAS mutations) can mediate resistance to EGFR inhibition; thus, dual blockade may overcome this mechanism. This combination has been explored primarily in patients with NSCLC who develop acquired BRAF V600E or KRAS-G12V mutations after progression on osimertinib[8]. Early studies suggest potential efficacy in overcoming such resistance mechanisms[8].

Other names

osimertinib + trametinib