Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 03 2022
14 03 2022
Historique:
received:
18
08
2021
accepted:
16
02
2022
entrez:
15
3
2022
pubmed:
16
3
2022
medline:
6
4
2022
Statut:
epublish
Résumé
High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31-0.66) and a median PFS of 7.6 months (90% CI: 3.4-12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.
Identifiants
pubmed: 35289329
doi: 10.1038/s41467-022-29052-7
pii: 10.1038/s41467-022-29052-7
pmc: PMC8921328
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT03279692']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1325Subventions
Organisme : NCI NIH HHS
ID : R01 CA227156
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244975
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA220253
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Informations de copyright
© 2022. The Author(s).
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