LAUSR

9030Background: EGFR exon 20 insertions (Ex20Ins), the 3rd most common EGFR activating mutation, are generally unresponsive to 1st and 2nd generation EGFR-TKIs. Development of EGFR-TKIs that effectively target NSCLC with Ex20Ins mutations represents a major unmet need. Osimertinib is an EGFR TKI approved for the treatment of advanced NSCLC harboring EGFR T790M, but the potential of osimertinib remains to be fully assessed in patients (pts) with Ex20Ins NSCLC. Methods: CRISPR engineered Ex20Ins cell line xenografts representing the two most common Ex20Ins (D770_N771InsSVD and V769_D770InsASV) and pt derived xenograft (PDX) of 3 EGFR Ex20Ins (V769_D770InsASV, M766_A767insASV, H773_V774insNPH) were used for in vivo experiments. Xenografts were treated by oral gavage with vehicle, erlotinib (50 mg/kg/day) or afatinib (20 mg/kg/day), osimertinib metabolite AZ5104 (50 mg/kg/day) and osimertinib (25 mg/kg/day) and assessed for tumor growth inhibition (TGI). Immunoblotting was performed for EGFR and relevant sign...