Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study
Henrik Jespersen,
Roger Olofsson Bagge,
Gustav Ullenhag,
Ana Carneiro,
Hildur Helgadottir,
Ingrid Ljuslinder,
Max Levin,
Charlotta All-Eriksson,
Bengt Andersson,
Ulrika Stierner,
Lisa M. Nilsson,
Jonas A. Nilsson,
Lars Ny
Affiliations
Henrik Jespersen
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Roger Olofsson Bagge
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Gustav Ullenhag
Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University
Ana Carneiro
Department of Oncology, Skåne University Hospital
Hildur Helgadottir
Department of Oncology, Karolinska University Hospital
Ingrid Ljuslinder
Department of Oncology, Norrlands University Hospital
Max Levin
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Charlotta All-Eriksson
St. Erik Eye Hospital
Bengt Andersson
Department of Clinical immunology and transfusion medicine, Sahlgrenska University Hospital
Ulrika Stierner
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Lisa M. Nilsson
Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Jonas A. Nilsson
Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Lars Ny
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital
Abstract 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 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24 months. 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.
