Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Autor: | 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 |
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Rok vydání: | 2022 |
Předmět: |
Lung Neoplasms
Oncology and Carcinogenesis Antineoplastic Agents Article Antibodies Clinical Research Carcinoma Non-Small-Cell Lung Insertional Antibodies Bispecific Humans Non-Small-Cell Lung Protein Kinase Inhibitors Lung Cancer Carcinoma Lung Cancer Evaluation of treatments and therapeutic interventions Exons ErbB Receptors Mutagenesis Insertional Oncology Mutagenesis 5.1 Pharmaceuticals 6.1 Pharmaceuticals Mutation Bispecific Development of treatments and therapeutic interventions |
Zdroj: | Cancer discovery, vol 12, iss 7 Cancer Discov |
Popis: | 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 |
Databáze: | OpenAIRE |
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