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Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study
Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Oncol,Sahlgrenska Acad, Bla Straket 2, S-41345 Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Surg,Sahlgrenska Acad, Bla Straket 5, S-41345 Gothenburg, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Skane Univ Hosp, Dept Oncol, Getingevagen 4, S-22185 Lund, Sweden.
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 415Article in journal (Refereed) Published
Abstract [en]

Background: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.

Methods: The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.

Discussion: The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.Trial registration

ClinicalTrials.gov registration number: NCT02697630. (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 19, article id 415
Keywords [en]
Uveal melanoma, Metastatic, Immunotherapy, Programmed cell death 1 receptor, Pembrolizumab, Epigenetics, Histone deacetylase inhibitors, Entinostat
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-383839DOI: 10.1186/s12885-019-5623-3ISI: 000466882500003PubMedID: 31046743OAI: oai:DiVA.org:uu-383839DiVA, id: diva2:1318140
Funder
Knut and Alice Wallenberg FoundationSwedish Cancer SocietyBioCARE - Biomarkers in Cancer Medicine Improving Health Care Education and InnovationAvailable from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-05-27Bibliographically approved

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