Abstract P02-04: BDTX-1535, a CNS penetrant MasterKey inhibitor of common, uncommon and resistant EGFR mutations, demonstrates in vivo efficacy and has potential to treat osimertinib-resistant NSCLC with or without brain metastases

NSCLC accounts for approximately 85% of lung cancer cases worldwide. NSCLC harboring EGFR mutations constitutes 10-20% of all lung cancer cases in Europe and North America, and up to 50% of those in Asia. The majority (80-90%) of these mutations are either Exon19del or L858R. Uncommon EGFR mutations, of which G719X, S768I and L861Q are amongst the most frequent, account for 10-20% of EGFR mutations in NSCLC. Additionally, secondary EGFR mutations such as C797S that emerge during treatment with osimertinib occur in ~10% of patients. Current generation EGFR inhibitors with efficacy against common, uncommon and/or resistance mutations are either poorly brain penetrant or do not have broad spectrum activity against multiple mutations. BDTX-1535 is an irreversible, spectrum selective MasterKey inhibitor of common, uncommon and resistance EGFR mutations such as G719X and C797S that occur in NSCLC (IC50 Citation Format: Matthew C. Lucas, Melinda S. Merchant, Matthew O'Connor, Carl Cook, Sherri Smith, Anthony Trombino, Wu-Yan Zhang, Irache Visiers, Kate Tith, Reza Foroughi, Nigel Waters, Iwona Wrona, Michael Pickard, Sudharshan Eathiraj, Karsten Witt, Christopher Roberts, Rachel Humphrey, Elizabeth Buck. BDTX-1535, a CNS penetrant MasterKey inhibitor of common, uncommon and resistant EGFR mutations, demonstrates in vivo efficacy and has potential to treat osimertinib-resistant NSCLC with or without brain metastases [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P02-04.