384P BLU-945, a Highly Potent and Selective 4th Generation EGFR TKI for the Treatment of EGFR T790M/C797S Resistant NSCLC

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR-mutant (L858R and ex19del) driven non-small-cell lung cancer (NSCLC). T790M is the most prevalent acquired EGFR resistance mutation to treatment with 1st and 2nd generation TKIs. 3rd generation TKIs, such as osimertinib, were developed to treat patients with tumors driven by this mutation. The C797S mutation is the most significant on-target resistance mechanism to osimertinib, leading to EGFR T790M/C797S double-resistant mutants.