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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

Ny, Lars ; Jespersen, Henrik ; Karlsson, Joakim ; Alsén, Samuel ; Filges, Stefan ; All-Eriksson, Charlotta ; Andersson, Bengt ; Carneiro, Ana LU orcid ; Helgadottir, Hildur and Levin, Max , et al. (2021) In Nature Communications 12(1).
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
5155
publisher
Nature Publishing Group
external identifiers
  • pmid:34453044
  • scopus:85113742815
ISSN
2041-1723
DOI
10.1038/s41467-021-25332-w
language
English
LU publication?
yes
id
b278d4ed-ac7d-45cb-a982-67bd3ba733b3
date added to LUP
2021-09-17 12:58:18
date last changed
2024-06-16 19:02:26
@article{b278d4ed-ac7d-45cb-a982-67bd3ba733b3,
  abstract     = {{<p>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.</p>}},
  author       = {{Ny, Lars and Jespersen, Henrik and Karlsson, Joakim and Alsén, Samuel and Filges, Stefan and All-Eriksson, Charlotta and Andersson, Bengt and Carneiro, Ana and Helgadottir, Hildur and Levin, Max and Ljuslinder, Ingrid and Olofsson Bagge, Roger and Sah, Vasu R. and Stierner, Ulrika and Ståhlberg, Anders and Ullenhag, Gustav and Nilsson, Lisa M. and Nilsson, Jonas A.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-25332-w}},
  doi          = {{10.1038/s41467-021-25332-w}},
  volume       = {{12}},
  year         = {{2021}},
}