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

Author

Listed:
  • Lars Ny

    (University of Gothenburg and Sahlgrenska University Hospital)

  • Henrik Jespersen

    (University of Gothenburg and Sahlgrenska University Hospital
    Akershus University Hospital)

  • Joakim Karlsson

    (University of Gothenburg and Sahlgrenska University Hospital
    University of Western Australia)

  • 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
    University of Western Australia)

  • Jonas A. Nilsson

    (University of Gothenburg and Sahlgrenska University Hospital
    University of Western Australia)

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.

Suggested Citation

  • Lars Ny & Henrik Jespersen & Joakim Karlsson & Samuel Alsén & Stefan Filges & Charlotta All-Eriksson & Bengt Andersson & Ana Carneiro & Hildur Helgadottir & Max Levin & Ingrid Ljuslinder & Roger Olofs, 2021. "The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25332-w
    DOI: 10.1038/s41467-021-25332-w
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    Cited by:

    1. Gaoyang Liang & Tae Gyu Oh & Nasun Hah & Hervé Tiriac & Yu Shi & Morgan L. Truitt & Corina E. Antal & Annette R. Atkins & Yuwenbin Li & Cory Fraser & Serina Ng & Antonio F. M. Pinto & Dylan C. Nelson , 2023. "Inhibiting stromal Class I HDACs curbs pancreatic cancer progression," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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