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Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC

Authors
 Misako Nagasaka  ;  Viola W Zhu  ;  Sun Min Lim  ;  Michael Greco  ;  Fengying Wu  ;  Sai-Hong Ignatius Ou 
Citation
 JOURNAL OF THORACIC ONCOLOGY, Vol.16(5) : 740-763, 2021-05 
Journal Title
JOURNAL OF THORACIC ONCOLOGY
ISSN
 1556-0864 
Issue Date
2021-05
MeSH
Acrylamides ; Aniline Compounds ; China ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; ErbB Receptors / genetics ; Humans ; Lung Neoplasms* / drug therapy ; Morpholines ; Mutation ; Protein Kinase Inhibitors* / therapeutic use ; Pyrazoles ; Pyrimidines
Keywords
Alflutinib ; Almonertinib ; Furmonertinib ; Lazertinib ; Osimertinib ; Rezivertinib ; T790M
Abstract
Single-agent osimertinib is the standard of care for the first-line treatment of advancedEGFR+ NSCLC and remained the only marketed third-generation EGFR tyrosine kinase inhibitor (TKI) until March 2020 when almonertinib (HS-10296) was approved in the People's Republic of China for the treatment of advanced EGFR T790M+ NSCLC based on a phase 2 expansion study of a phase 1/2 trial. In this review, we profiled many of the third-generation EGFR TKIs in late-stage clinical development (e.g., almonertinib, lazertinib, alflutinib1, rezivertinib, ASK120069, SH-1028, D-0316, and abivertinib) based on their interim results from phase 1 and phase 2 trials, and included the designs of the phase 3 trials and their chemical structures when publicly available. We also listed other third-generation EGFR TKIs in pipeline development based on the search of clinical trial registration websites. In addition, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, mavelertinib), including phase 3 results of rociletinib and naquotinib. We further profiled combination clinical trial design of the third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704), and ACROSS2 (NCT04500717) that if positive can potentially usher in the next standard of care for advanced EGFR+ NSCLC.
DOI
10.1016/j.jtho.2020.11.028
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lim, Sun Min(임선민)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190935
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