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

Lars Ny (), Henrik Jespersen, Joakim Karlsson, Samuel Alsén, Stefan Filges, Charlotta All-Eriksson, Bengt Andersson, Ana Carneiro, Hildur Helgadottir, Max Levin, Ingrid Ljuslinder, Roger Olofsson Bagge, Vasu R. Sah, Ulrika Stierner, Anders Ståhlberg, Gustav Ullenhag, Lisa M. Nilsson and Jonas A. Nilsson ()
Additional contact information
Lars Ny: University of Gothenburg and Sahlgrenska University Hospital
Henrik Jespersen: University of Gothenburg and Sahlgrenska University Hospital
Joakim Karlsson: University of Gothenburg and Sahlgrenska University Hospital
Samuel Alsén: University of Gothenburg and Sahlgrenska University Hospital
Stefan Filges: University of Gothenburg and Sahlgrenska University Hospital
Charlotta All-Eriksson: St. Erik Eye Hospital
Bengt Andersson: Sahlgrenska University Hospital
Ana Carneiro: Skåne University Hospital, and Institute of Clinical Sciences, Lund University
Hildur Helgadottir: Karolinska University Hospital
Max Levin: University of Gothenburg and Sahlgrenska University Hospital
Ingrid Ljuslinder: Norrlands University Hospital
Roger Olofsson Bagge: University of Gothenburg and Sahlgrenska University Hospital
Vasu R. Sah: University of Gothenburg and Sahlgrenska University Hospital
Ulrika Stierner: University of Gothenburg and Sahlgrenska University Hospital
Anders Ståhlberg: University of Gothenburg and Sahlgrenska University Hospital
Gustav Ullenhag: Uppsala University Hospital
Lisa M. Nilsson: University of Gothenburg and Sahlgrenska University Hospital
Jonas A. Nilsson: University of Gothenburg and Sahlgrenska University Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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 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.

Date: 2021
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DOI: 10.1038/s41467-021-25332-w

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