Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Mengzhao Wang, James Chih Hsin Yang, Paul L. Mitchell, Jian Fang, D. Ross Camidge, Weiqi Nian, Chao Hua Chiu, Jianying Zhou, Yanqiu Zhao, Wu Chou Su, Tsung Ying Yang, Viola W. Zhu, Michael Millward, Yun Fan, Wen Tsung Huang, Ying Cheng, Liyan Jiang, Daniel Brungs, Lyudmila Bazhenova, Chee Khoon LeeBo Gao, Yan Xu, Wei Hsun Hsu, Li Zheng, Pasi A. Jänne

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Epidermal growth factor receptor exon 20 insertion mutations (EGFRexon20ins) are detected in approximately 2% of patients with non–small cell lung cancer (NSCLC). Due to a lack of effective therapy, the prognosis of these patients is typically poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible, and selective EGFR tyrosine kinase inhibitor, showing activity against EGFRexon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase I 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 EGFRexon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response has not been reached. SIGNIFICANCE: We report the discovery and early clinical development of sunvozertinib, a potential treatment option for the unmet medical need of EGFRexon20ins NSCLC.

Original languageEnglish
Pages (from-to)1676-1689
Number of pages14
JournalCancer Discovery
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 2022
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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