BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

Resistance to third-generation EGFR inhibitors including osimertinib arises in part from the C797S mutation in EGFR. Currently, no targeted treatment option is available for these patients. We have developed a new EGFR tyrosine kinase inhibitor (TKI), BBT-176, targeting the C797S mutation.

Patients and methods

Recombinant EGFR proteins and Ba/F3 cell lines, patient-derived cells, and patient-derived xenografts expressing mutant EGFRs were used to test the inhibitory potency and the anticancer efficacy of BBT-176 both in vitro and in vivo. Patient case data are also available from an ongoing phase I clinical trial (NCT04820023).

Results

The half maximal inhibitory concentration (IC50) of BBT-176 against EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, and EGFR L858R/C

SUBMITTER: Lim SM 

PROVIDER: S-EPMC10425724 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature