TY - JOUR
T1 - The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
AU - Ny, Lars
AU - Jespersen, Henrik
AU - Karlsson, Joakim
AU - Alsén, Samuel
AU - Filges, Stefan
AU - All-Eriksson, Charlotta
AU - Andersson, Bengt
AU - Carneiro, Ana
AU - Helgadottir, Hildur
AU - Levin, Max
AU - Ljuslinder, Ingrid
AU - Olofsson Bagge, Roger
AU - Sah, Vasu R.
AU - Stierner, Ulrika
AU - Ståhlberg, Anders
AU - Ullenhag, Gustav
AU - Nilsson, Lisa M.
AU - Nilsson, Jonas A.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113742815&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25332-w
DO - 10.1038/s41467-021-25332-w
M3 - Article
C2 - 34453044
AN - SCOPUS:85113742815
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5155
ER -