Evidence map›Paper›PMID 40858103›Full record

ArticleCell reports. Medicine2025

AZ14289671 is a highly selective and blood-brain barrier penetrant irreversible TKI that targets EGFRExon20 insertions.

Aisha M Swaih, Sara Talbot, Adriana Savoca, Hannah Thorpe, Vikki Flemington, Benjamin Phillips, Nicola Colclough, William McCoull, Veronika Radeva, David Hargreaves and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Aisha M SwaihBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Sara TalbotBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Adriana SavocaClinical Pharmacology and Safety Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Hannah ThorpeBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Vikki FlemingtonBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Benjamin PhillipsDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Nicola ColcloughDMPK, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
William McCoullChemistry, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Veronika RadevaBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
David HargreavesDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Martin J PackerChemistry, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Catarina Felisberto-RodriguesDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Clare ThomsonChemistry, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Jonathan P OrmeDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Carly DeaneDMPK, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Aaron SmithDMPK, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Peter JohnströmPET Science Centre, Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Stockholm 171 76, Sweden.
Magnus SchouPET Science Centre, Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Stockholm 171 76, Sweden.
Lisa McWilliamsDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Paul DaveyChemistry, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Marianne EngetChemistry, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Daniel O'NeillDiscovery Sciences, BioPharmaceutical R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Sabina CosulichEarly Oncology Development, Oncology R&D AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK.
Nicolas Floc'hBioscience, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK. Electronic address: nicolas.floch@astrazeneca.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current clinical therapeutics against non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (EGFRExon20Ins) mutations yield limited responses particularly against brain metastases; therefore, there is a need for an effective tyrosine kinase inhibitor (TKI). AZ14289671 is an oral, potent, irreversible, selective, and blood-brain barrier penetrant TKI targeting EGFRExon20Ins mutations while sparing wild-type (WT) EGFR. Preclinical assessments using cell lines, cell line-derived xenograft, and patient-derived xenograft models harboring EGFRExon20Ins demonstrate that AZ14289671 exhibits strong signaling pathway inhibition and highly sustained tumor regression against multiple EGFRExon20Ins, whereas its activity against WT is minimal. Additionally, AZ14289671 can cross the blood-brain barrier. This has the potential to improve outcomes of NSCLC patients with EGFRExon20Ins.

Indexed as

Blood-Brain BarrierCarcinoma, Non-Small-Cell LungLung NeoplasmsProtein Kinase InhibitorsAnimalsCell Line, TumorErbB ReceptorsExonsFemaleHumansMiceMice, NudeMutagenesis, InsertionalXenograft Model Antitumor AssaysEGFR protein, humanErbB ReceptorsProtein Kinase InhibitorsEGFRexon 20 insertionsNSCLCsmall molecule inhibitor

Identifiers

PMID40858103
PMCPMC12490212

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.