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 (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. This article is highlighted in the In This Issue feature, p. 1599.

• Authors: 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 Lee, Bo Gao, Yan Xu, Wei-Hsun Hsu, Li Zheng, Pasi A Jänne
• Journal: Cancer discovery (Cancer Discov) Vol. 12 Issue 7 Pg. 1676-1689 (07 06 2022) ISSN: 2159-8290 [Electronic] United States
• PMID: 35404393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Antibodies, Bispecific
• Antineoplastic Agents
• Protein Kinase Inhibitors
• amivantamab-vmjw
• EGFR protein, human
• ErbB Receptors

Topics

• Antibodies, Bispecific
• Antineoplastic Agents (adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• ErbB Receptors (genetics)
• Exons
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Mutagenesis, Insertional
• Mutation
• Protein Kinase Inhibitors (pharmacology, therapeutic use)