On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
02
05
2019
revised:
12
07
2019
accepted:
07
10
2019
pubmed:
18
10
2019
medline:
12
1
2021
entrez:
18
10
2019
Statut:
ppublish
Résumé
The PI3K inhibitor copanlisib has efficacy and manageable safety in patients with indolent lymphoma and solid tumors. Pharmacodynamic effects relative to copanlisib dose and plasma exposure were evaluated. Patients with lymphoma or solid tumors received copanlisib 0.4 or 0.8 mg/kg on days 1, 8, and 15 of a 28-day cycle. Primary variables were maximum changes in phosphorylated AKT (pAKT) levels in platelet-rich plasma (PRP) and plasma glucose. Other evaluations included PI3K signaling markers and T-lymphocytes in paired tumor biopsies, the relationship between estimated plasma exposure and pharmacodynamic markers, response, and safety. Sixty-three patients received copanlisib. PRP pAKT levels showed sustained reductions from baseline following copanlisib [median inhibition: 0.4 mg/kg, 73.8% (range -94.9 to 144.0); 0.8 mg/kg, 79.6% (range -96.0 to 408.0)]. Tumor pAKT was reduced versus baseline with copanlisib 0.8 mg/kg in paired biopsy samples (
Identifiants
pubmed: 31619463
pii: 1535-7163.MCT-19-0466
doi: 10.1158/1535-7163.MCT-19-0466
doi:
Substances chimiques
Pyrimidines
0
Quinazolines
0
copanlisib
WI6V529FZ9
Banques de données
ClinicalTrials.gov
['NCT03711058']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
468-478Informations de copyright
©2019 American Association for Cancer Research.