@article{249e4ba419774e1d8fc02725714881ac,
title = "Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations",
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.",
author = "Mengzhao Wang and Yang, {James Chih Hsin} and Mitchell, {Paul L.} and Jian Fang and Camidge, {D. Ross} and Weiqi Nian and Chiu, {Chao Hua} and Jianying Zhou and Yanqiu Zhao and Su, {Wu Chou} and Yang, {Tsung Ying} and Zhu, {Viola W.} and Michael Millward and Yun Fan and Huang, {Wen Tsung} and Ying Cheng and Liyan Jiang and Daniel Brungs and Lyudmila Bazhenova and Lee, {Chee Khoon} and Bo Gao and Yan Xu and Hsu, {Wei Hsun} and Li Zheng and J{\"a}nne, {Pasi A.}",
note = "Funding Information: This study was sponsored by Dizal Pharmaceuticals. Some of this work was supported in part by grants from the Wuxi Municipal Bureau on Science and Technology (WX03-02B0105-062000-01; to L. Zheng) on the WU-KONG2 study. Funding Information: M. Wang reports a consultant role with Dizal Pharmaceuticals. J.C.-H. Yang reports personal fees and other support from Daiichi Sankyo, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche/ Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Amgen, Bayer, Boehringer Ingelheim, and Bristol Myers Squibb, grants, personal fees, and other support from AstraZeneca, other support from Puma Technology and Eli Lilly, and personal fees from Ono Pharmaceutical, Gilead, and GSK outside the submitted work. P.L. Mitchell reports personal fees from Roche, MSD, Amgen, AstraZeneca, Bristol Myers Squibb, Lilly, Novartis, Pfizer, and Puma Biotechnology outside the submitted work. D.R. Camidge reports institutional support for the Dizal Pharmaceuticals trial. C.-H. Chiu reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Takeda, and Amgen outside the submitted work. V.W. Zhu reports other support from AstraZeneca, Blueprint, Nuvalent, Roche Foundation Medicine, Roche/Genentech, Takeda, TP Therapeutics, and Xcovery outside the submitted work. M. Millward reports other support from Dizal Pharmaceuticals during the conduct of the study, as well as personal fees from Merck Sharp & Dohme, Takeda Pharmaceuticals, Bristol Myers Squibb, Roche Products, Pfizer Australia, Novartis Pharma AG, Amgen Australia, Limbic, Merck Pte. Ltd., Beigene Australia, and Guardant Health and nonfinancial support from AstraZeneca outside the submitted work. L. Bazhenova reports AstraZeneca, Genen-tech, Beyondspring, Takeda, Bluprint Pharma, Novartis, Boehringer Ingelheim, Regeneron, Merck, Bristol Myers Squibb, Janssen, Daichi Sankyo, Neuvogen, Turning Point Therapeutics, Sanofi, Bayer, Mirati, Novovure, and ORIC outside the submitted work. C.K. Lee reports other support from Dizal Pharmaceuticals during the conduct of the study, as well as grants and personal fees from AstraZeneca, Roche, Amgen, and Merck KGaA, and personal fees from Takeda, Yuhan, Pfizer, MSD Oncology, GSK, Novartis, Janssen, and Boehringer Ingel-heim outside the submitted work. Y. Xu reports grants from AstraZeneca outside the submitted work. W.-H. Hsu reports personal fees from AstraZeneca, Roche, Pfizer, Eli Lilly, Chugai, Takeda, Ono, Amgen, Jassen, ACT Genomics, MSD, and Guardant Health outside the submitted work. L. Zheng is an employee of and a shareholder in Dizal Pharmaceuticals. P.A. J{\"a}nne reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai, SFJ Pharmaceuticals, Voronoi, Biocartis, Novartis, Sanofi Oncology, Mirati Therapeutics, Transcenta, Silicon Therapeutics, Syndax, Nuva-lent, Bayer, Esai, Allorion Therapeutics, Accutar Biotech, AbbVie, Eli Lilly, Daiichi Sankyo, and Takeda Oncology, and grants from Revolution Medicines and Puma outside the submitted work, as well as a patent for EGFR mutations issued, licensed, and with royalties paid from LabCorp. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2022 TheAuthors; Published by the American Association for Cancer Research.",
year = "2022",
month = jul,
doi = "10.1158/2159-8290.CD-21-1615",
language = "English",
volume = "12",
pages = "1676--1689",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}
