Abstract 5871: Discovery and characterization of firmonertinib, a novel EGFR inhibitor with broad activity against both EGFR classical and exon 20 insertion mutations

Abstract Background: Lung cancers harboring classical EGFR mutations are sensitive to approved EGFR tyrosine kinase inhibitors (TKIs) while those harboring EGFR exon 20 insertion mutations (ex20ins) show minimal sensitivity to approved EGFR TKIs and have limited treatment options. Firmonertinib is an investigational novel orally bioavailable and highly brain-penetrant irreversible EGFR TKI targeting classical and uncommon EGFR mutations including ex20ins. Firmonertinib received FDA Breakthrough Therapy Designation for first-line treatment of patients with advanced NSCLC with EGFR ex20ins mutations, and has now completed enrollment in a global phase 3 trial in these patients (NCT05607550). Here, we describe the structural and preclinical findings supporting the binding potency and anti-tumor activity of firmonertinib in EGFR ex20ins mutations. Methods Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5871.