Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Year: 2022
Type: article
Study design: Clinical Trial
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.
Source: Cancer Discovery
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
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital, National Taiwan University, National Taiwan University Hospital, Austin Hospital, Peking University Cancer Hospital, University of Colorado Cancer Center, University of Colorado Anschutz, Chongqing Cancer Hospital, Taipei Veterans General Hospital, Zhejiang University, Zhengzhou University, National Cheng Kung University Hospital, Taichung Veterans General Hospital, University of California, Irvine Medical Center, UC Irvine Chao Family Comprehensive Cancer Center, Linear Clinical Research, Zhejiang Cancer Hospital, Chi Mei Medical Center, Jilin Province Tumor Hospital, Shanghai Chest Hospital, University of California San Diego, Moores Cancer Center, St George Hospital, Blacktown & Mount Druitt Hospital, Dizal (Jiangsu) Pharmaceutical Co., Ltd. (China), Dana-Farber Cancer Institute
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4223521674