Dizal announced new findings from a biomarker study in non-small cell lung cancer (NSCLC) patients with exon 20 insertion (exon20ins) mutations, highlighting sunvozertinib as an effective treatment for this patient population. The findings have been published in an abstract (#8563) available on the official website of the 2024 American Society of Clinical Oncology's (ASCO) Annual Meeting. A total of 121 patients with EGFR exon20ins mutations treated with sunvozertinib were included in this biomarker study.

Serial plasma ctDNA samples were collected from baseline until disease progression (PD). The key findings of the analysis were as follows: There was a positive correlation between detectable EGFR exon20ins in baseline plasma ctDNA and higher number of metastasis sites. Higher abundance of EGFR exon20ins in baseline plasma ctDNA was positively correlated with more metastasis sites and brain metastasis (BM).

Patients with baseline negative EGFR exon20ins in plasma ctDNA achieved a higher objective response rate (ORR) (68.0% vs. 45.8%) and longer median progression free survival (PFS) (7.4 months vs. 5.5 months) than those with positive EGFR exon20ins.

Decrease of EGFR exon20ins mutant allele was observed in 85.7% of patients with sunvozertinib treatment. The earliest clearance of EGFR exon20ins occurred after one week of sunvozertinib treatment. Acquired EGFR C797S and other genetic aberrations in EGFR downstream signaling pathway may be associated with resistance to sunvozertinib.

In vitro and in vivo experiments suggested that combination of golidocitinib, a JAK1 inhibitor, with chemotherapy could be a potential approach to overcome sunvozertinib resistance.