1. Sunvozertinib, a selective EGFR inhibitor for previously treated non-small cell lung cancer with EGFR exon 20 insertion mutationsSunvozertinib for NSCLC with EGFR Exon20ins
- Author
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Wang, Mengzhao, Yang, James Chih-Hsin, Mitchell, Paul L, Fang, Jian, Camidge, D Ross, Nian, Weiqi, Chiu, Chao-Hua, Zhou, Jianying, Zhao, Yanqiu, Su, Wu-Chou, Yang, Tsung-Ying, Zhu, Viola W, Millward, Michael, Fan, Yun, Huang, Wen-Tsung, Cheng, Ying, Jiang, Liyan, Brungs, Daniel, Bazhenova, Lyudmila, Lee, Chee Khoon, Gao, Bo, Xu, Yan, Hsu, Wei-Hsun, Zheng, Li, and Janne, Pasi A
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Lung Cancer ,Clinical Research ,Lung ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Antibodies ,Bispecific ,Antineoplastic Agents ,Carcinoma ,Non-Small-Cell Lung ,ErbB Receptors ,Exons ,Humans ,Lung Neoplasms ,Mutagenesis ,Insertional ,Mutation ,Protein Kinase Inhibitors ,Biochemistry and cell biology ,Oncology and carcinogenesis - 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.SignificanceWe 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.
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- 2022