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@ARTICLE{Heymach:309658,
author = {J. V. Heymach and S. Popat and E. F. Smit and P.
Christopoulos$^*$ and D. Planchard and T. Yoshida and J.
Zugazagoitia and Y. Yu and B. Wilding},
title = {{T}he role of zongertinib, a highly selective tyrosine
kinase inhibitor, in targeting {HER}2-mutant {NSCLC}: a
bench-to-bedside review.},
journal = {Expert review of anticancer therapy},
volume = {nn},
issn = {1473-7140},
address = {Abingdon, Oxon},
publisher = {Taylor $\&$ Francis},
reportid = {DKFZ-2026-00290},
pages = {nn},
year = {2026},
note = {#NCTZFB9# / epub},
abstract = {HER2 is mutated in $2-4\%$ of non-small cell lung cancers
(NSCLC) and is associated with poor prognosis. Tyrosine
kinase inhibitors (TKIs) targeting HER2 have historically
been hampered by insufficient efficacy against exon 20
insertion mutations and lack of specificity, resulting in
off-target adverse events. Zongertinib is an oral,
irreversible HER2-selective TKI that spares wild-type EGFR,
thereby minimizing associated toxicities. Zongertinib was
recently approved in the United States (accelerated), China
(conditional), and Japan for patients with previously
treated advanced HER2-mutant NSCLC.This article outlines the
discovery and clinical development of zongertinib that led
to these approvals. We discuss the first-in-human Beamion
LUNG-1 trial (NCT04886804), in which zongertinib
demonstrated encouraging and durable activity, with a
manageable safety profile, in patients with HER2-mutant
advanced NSCLC. Finally, we summarize ongoing clinical
trials of zongertinib, including its assessment as
first-line treatment for advanced HER2-mutant
NSCLC.Zongertinib is the first oral TKI approved for
HER2-mutant NSCLC and will provide patients with a
convenient, tolerable and effective treatment option in an
area of significant unmet need. Next steps include its
potential transition to a first-line setting, identification
of additional indications, and development of novel
combination regimens.},
subtyp = {Review Article},
keywords = {Zongertinib (Other) / human epidermal growth factor
receptor 2 (Other) / non-small cell lung cancer (Other) /
targeted therapy (Other) / tyrosine kinase inhibitor
(Other)},
cin = {HD02},
ddc = {610},
cid = {I:(DE-He78)HD02-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41640088},
doi = {10.1080/14737140.2026.2623059},
url = {https://inrepo02.dkfz.de/record/309658},
}