Abstract
This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.
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•EGFR exon20ins positive in ctDNA is associated with advanced disease characteristics•Sunvozertinib can effectively clear EGFR exon20ins in ctDNA•Resistance to sunvozertinib can be through EGFR-dependent and -independent mechanisms
Xu et al. show that EGFR exon20ins positivity and higher EGFR exon20ins abundance in ctDNA are correlated with advanced NSCLC. The earliest clearance of EGFR exon20ins in ctDNA occurs after 1 week of sunvozertinib treatment. Acquired EGFR C797S is a potential on-target resistance mutation to sunvozertinib.