Sunvozertinib, a selective EGFR inhibitor for previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations.

Abstract

Epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) are detected in approximately 2% of patients with non-small cell lung cancer (NSCLC). Due to lack of effective therapy, the prognosis of these patients was poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible and selective EGFR tyrosine kinase inhibitor, showing activity against EGFR exon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase 1 clinical studies, sunvozertinib was tolerated up to 400 mg once daily. The most common drug-related adverse events included diarrhea and skin rash. Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFR exon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response (DoR) has not been reached.