Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study) : Protocol for a multicenter phase II open label study
(2019) In BMC Cancer 19(1).- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2019-05-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Entinostat, Epigenetics, Histone deacetylase inhibitors, Immunotherapy, Metastatic, Pembrolizumab, Programmed cell death 1 receptor, Uveal melanoma
- in
- BMC Cancer
- volume
- 19
- issue
- 1
- article number
- 415
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85065166603
- pmid:31046743
- ISSN
- 1471-2407
- DOI
- 10.1186/s12885-019-5623-3
- language
- English
- LU publication?
- yes
- id
- be9fc2ee-c321-4ebe-9760-e403843e36c0
- date added to LUP
- 2019-05-21 13:32:32
- date last changed
- 2024-09-03 19:34:13
@article{be9fc2ee-c321-4ebe-9760-e403843e36c0, abstract = {{<p>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.</p>}}, author = {{Jespersen, Henrik and Bagge, Roger Olofsson and Ullenhag, Gustav and Carneiro, Ana and Helgadottir, Hildur and Ljuslinder, Ingrid and Levin, Max and All-Eriksson, Charlotta and Andersson, Bengt and Stierner, Ulrika and Nilsson, Lisa M. and Nilsson, Jonas A. and Ny, Lars}}, issn = {{1471-2407}}, keywords = {{Entinostat; Epigenetics; Histone deacetylase inhibitors; Immunotherapy; Metastatic; Pembrolizumab; Programmed cell death 1 receptor; Uveal melanoma}}, language = {{eng}}, month = {{05}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, series = {{BMC Cancer}}, title = {{Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study) : Protocol for a multicenter phase II open label study}}, url = {{http://dx.doi.org/10.1186/s12885-019-5623-3}}, doi = {{10.1186/s12885-019-5623-3}}, volume = {{19}}, year = {{2019}}, }