Sunvozertinib是一种选择性EGFR抑制剂

Sunvozertinib, a selective EGFR inhibitor for previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations

(Cancer Discovery, IF: 39.397)

• 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

Abstract 摘要

Epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) are detected in approximately 2% of patients with non-small cell lung cancer (NSCLC). Due to lack of effective therapy, the prognosis of these patients was poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible and selective EGFR tyrosine kinase inhibitor, showing activity against EGFR exon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase 1 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 EGFR exon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response (DoR) has not been reached.

约2%的非小细胞肺癌（NSCLC）患者中检测到表皮生长因子受体外显子20插入突变（EGFR exon20ins）。由于缺乏有效的治疗，这些患者的预后很差。Sunvozertinib（DZD9008）是一种口服、强效、不可逆和选择性EGFR酪氨酸激酶抑制剂，对EGFR exon20ins突变和其他突变具有活性。在细胞系和异种移植模型中，sunvozertinib显示出强大的抗肿瘤活性。在两项正在进行的1期临床研究中，sunvozertinib的耐受性高达400 mg，每日一次。最常见的药物相关不良事件包括腹泻和皮疹。在不同亚型EGFR exon20in突变的非小细胞肺癌患者中观察到应用100 mg及以上剂量的药物的抗肿瘤疗效，包括之前已使用amivantamab治疗以及基线脑转移。中位平均反应持续时间（DoR）尚未达到。

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