A phase 1 study of IDH305 in patients with IDH1
2-Hydroxyglutarate
Acute myeloid leukemia
IDH1
Isocitrate dehydrogenase
Myelodysplastic syndrome
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
02
02
2022
accepted:
10
03
2022
pubmed:
31
3
2022
medline:
8
3
2023
entrez:
30
3
2022
Statut:
ppublish
Résumé
Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). IDH305 is an orally bioavailable, brain-penetrant, mutant-selective allosteric IDH1 inhibitor demonstrating target engagement in preclinical models. This first-in human study was designed to identify the recommended dose for expansion/maximum tolerated dose of IDH305 in patients with IDH1 IDH305 was given at doses 75-750 mg twice daily in 41 patients with IDH1 IDH305 exhibited rapid absorption with mean T Due to potentially narrow therapeutic window, the study was prematurely halted and recommended phase 2 dose could not be declared. Clinicaltrials.gov identifier: NCT02381886.
Identifiants
pubmed: 35353219
doi: 10.1007/s00432-022-03983-6
pii: 10.1007/s00432-022-03983-6
doi:
Substances chimiques
Isocitrate Dehydrogenase
EC 1.1.1.41
Enzyme Inhibitors
0
IDH1 protein, human
EC 1.1.1.42.
Banques de données
ClinicalTrials.gov
['NCT02381886']
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1145-1158Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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