2022 World Conference on Lung Cancer (ePosters)-EP08.02-085. In vitro Activity and Potential Resistance Mutations Against BI-4020, a 4th-generation EGFR-TKI

EP08.02-085. In vitro Activity and Potential Resistance Mutations Against BI-4020, a 4th-generation EGFR-TKI

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The study evaluated the in vitro activity and potential resistance mutations of BI-4020, a fourth-generation EGFR tyrosine kinase inhibitor (TKI). The researchers used Ba/F3 cells driven by EGFR mutations and wild-type EGFR cells to evaluate the activity of BI-4020. They observed that BI-4020 was effective against Ba/F3 cells with EGFR exon 19 deletion or L858R mutation, regardless of the presence of T790M and/or C797S mutations. However, it was less active against Ba/F3 cells with EGFR exon 20 insertion mutations. Several secondary, tertiary, or quaternary mutations were identified as potential resistance mechanisms to BI-4020, with E709G and L718Q mutations conferring high-level resistance when combined with L858R and L858R/C797S mutations, respectively. However, these secondary mutations did not confer high-level resistance when combined with EGFR exon 19 deletion. The researchers used ENU mutagenesis to obtain acquired resistant cells against BI-4020 and identified mutations involving codons E709, L718, K754, and T854. The study suggests that acquisition of exon 18 mutations (E709G and L718Q) may cause high-level resistance to BI-4020 when L858R is a sensitizing mutation. Overall, the findings indicate that BI-4020 shows promise as a fourth-generation EGFR-TKI and can inhibit triple mutations of activating mutation/T790M/C797S. Further research is needed to explore its potential clinical implications and efficacy in treating EGFR-mutant lung cancer.

Asset Subtitle

Kenichi Suda

Meta Tag

Speaker Kenichi Suda

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

BI-4020

EGFR tyrosine kinase inhibitor

in vitro activity

resistance mutations

Ba/F3 cells

EGFR mutations

exon 19 deletion

L858R mutation

T790M mutation

C797S mutation