Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with <i>EGFR</i> Exon 20 Insertion Mutations

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  • Mengzhao Wang
    1Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
  • James Chih-Hsin Yang
    2National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
  • Paul L. Mitchell
    3Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.
  • Jian Fang
    4Beijing Cancer Hospital, Beijing, China.
  • D. Ross Camidge
    5University of Colorado Hospital, Anschutz Cancer Pavilion, Aurora, Colorado.
  • Weiqi Nian
    6Chongqing Cancer Hospital, Chongqing, China.
  • Chao-Hua Chiu
    7Taipei Veteran General Hospital, Taipei, Taiwan.
  • Jianying Zhou
    8Zhejiang University Affiliated Hospital, Zhejiang, China.
  • Yanqiu Zhao
    9Affiliated Cancer Hospital of Zhengzhou University, Henan, China.
  • Wu-Chou Su
    10National Cheng Kung University Hospital, Tainan, Taiwan.
  • Tsung-Ying Yang
    11Taichung Veteran Hospital, Taichung, Taiwan.
  • Viola W. Zhu
    12University of California Irvine Medical Center (UCIMC), Chao Family Comprehensive Cancer Center, Orange, California.
  • Michael Millward
    13Linear Clinical Research Limited, Nedlands, Perth, Western Australia, Australia.
  • Yun Fan
    14Zhejiang Cancer Hospital, Zhejiang, China.
  • Wen-Tsung Huang
    15Chi Mei Chest Hospital, Tainan, Taiwan.
  • Ying Cheng
    16Jilin Cancer Hospital, Jilin, China.
  • Liyan Jiang
    17Shanghai Chest Hospital, Shanghai, China.
  • Daniel Brungs
    18Southern Medical Day Care Centre, Wollongong, New South Wales, Australia.
  • Lyudmila Bazhenova
    19University of California, San Diego (UCSD), Moores Cancer Center, La Jolla, California.
  • Chee Khoon Lee
    20St George Hospital, Kogarah, Sydney, New South Wales, Australia.
  • Bo Gao
    21Blacktown Hospital, Blacktown, Sydney, New South Wales, Australia.
  • Yan Xu
    1Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
  • Wei-Hsun Hsu
    22National Taiwan University Hospital, Taipei, Taiwan.
  • Li Zheng
    23Dizal Pharmaceuticals, Shanghai, China.
  • Pasi A. Jänne
    24Dana-Farber Cancer Institute, Boston, Massachusetts.

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title/> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>We report the discovery and early clinical development of sunvozertinib, a potential treatment option for the unmet medical need of EGFRexon20ins NSCLC.</jats:p> <jats:p>This article is highlighted in the In This Issue feature, p. 1599</jats:p> </jats:sec>

収録刊行物

  • Cancer Discovery

    Cancer Discovery 12 (7), 1676-1689, 2022-04-11

    American Association for Cancer Research (AACR)

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