The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 08 2021
27 08 2021
Historique:
received:
28
03
2021
accepted:
05
08
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
2
10
2021
Statut:
epublish
Résumé
Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.Trial registration ClinicalTrials.gov registration number: NCT02697630 (registered 3 March 2016). EudraCT registration number: 2016-002114-50.
Identifiants
pubmed: 34453044
doi: 10.1038/s41467-021-25332-w
pii: 10.1038/s41467-021-25332-w
pmc: PMC8397717
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
BAP1 protein, human
0
Benzamides
0
Pyridines
0
Tumor Suppressor Proteins
0
entinostat
1ZNY4FKK9H
pembrolizumab
DPT0O3T46P
Ubiquitin Thiolesterase
EC 3.4.19.12
Banques de données
ClinicalTrials.gov
['NCT02697630']
EudraCT
['2016-002114-50']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5155Informations de copyright
© 2021. The Author(s).
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