EP08.02-018 Phase 1/2 Study of BLU-451, a Small Molecule Inhibitor of EGFR, in EGFR Exon 20 Insertion-Mutant Incurable Advanced Cancers

Abstract

Oncogenic EGFR exon 20 insertion (ex20ins) mutations, found in ∼2% of non-small cell lung cancers (NSCLC) and a small percentage of other cancers, are generally not responsive to EGFR-targeted agents that have been approved for treatment of NSCLC with a common EGFR mutation, including L858R and exon 19 deletion. Similar to these more common types of EGFR-mutated NSCLC, central nervous system (CNS) metastases are a challenge with EGFR ex20ins mutant NSCLC and are associated with poor outcomes. While two EGFR ex20ins-targeting drugs were recently approved by the US Food and Drug Administration (amivantamab and mobocertinib), neither have established CNS activity.