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2966 A Phase II Trial Investigating the Combination of Pembrolizumab (PEM) and Entinostat (ENT) in Relapsed and Refractory (R/R) Hodgkin Lymphoma (HL)

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Biological, antibodies, Diseases, Hodgkin Lymphoma, Therapies, Combinations, checkpoint inhibitors, immunotherapy, Lymphoid Malignancies, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Gottfried von Keudell, MD, PhD1, David Sermer, MD1, Santosha Vardhana, MD, PhD1*, Deanna Cho1*, Erin Biggar, BA1*, Alison J. Moskowitz, MD1, Anita Kumar, MD1,2, Connie Lee Batlevi, MD, PhD1, Philip Caron, MD, PhD1, Audrey Hamilton, MD1*, Matthew J Matasar, MD, MS3, Steven M. Horwitz, MD1, Heiko Schöder, MD4*, Tira Bunyaviroch5*, Andrew D. Zelenetz, MD, PhD6, Ahmet Dogan, MD, PhD7, Venkatraman Seshan, PhD8*, Anas Younes, MD9 and Erel Joffe, MD, MSc1

1Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Medicine, Lymphoma Service, Memorial Sloan Kettering, Short Hills, NJ
3Department of Medicine, Lymphoma Service, Memorial Sloan-Kettering Cancer Center/New York Presbyterian, New York, NY
4Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
5Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
6Memorial Sloan Kettering Cancer Center, New York, NY
7Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
8Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
9AstraZeneca, New York, NY


Histone deacetylase (HDAC) inhibitors have single agent activity in various types of lymphoma. They restore antigen-specific immune recognition in cancer cells and modulate programmed cell death (PD)-1 expression. Preclinical studies have shown synergy with the combination of HDAC inhibitors and anti-PD-1 antibodies in murine models of various tumors. Herein, we present safety and efficacy data from a phase II trial investigating a novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R HL and FL.


Patients with R/R HL received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. Prior use of anti-PD-1 or HDAC inhibitor was allowed if there had been clinical benefit. Tumor assessment was evaluated using the RECIL criteria. The primary objective is 12-month progression-free survival (PFS).


At time of censoring on 7/31/20, 17 patients with HL have been enrolled, including 6 currently receiving therapy on study. The median number of prior therapies was 4 (2-17) including 7 (41%) refractory to most recent therapy. 11 (65%) received prior autologous stem cell transplant (ASCT), 8 (47%) received prior anti-PD1 antibody therapy, and 3 (18%) prior HDAC inhibitor therapy. Out of 16 evaluable patients, the overall response rate (ORR) was 94% and the complete response (CR) rate was 63%. Responding patients included 6 with prior anti-PD-1 antibody and 3 with prior HDAC inhibitor therapy. With a median duration of follow-up of 8.4 months, the 12-month PFS was 84% (66%-100%) and the median PFS was not reached. The median duration on treatment was 6.6 months (range 2.3-16.2 months) with discontinuations due to progression (n=2), toxicity (n=3), consolidation with transplant (n=3) or radiation (n=1), or withdrawal of consent (n=3). Out of a total of 25 patients enrolled in this study (including an additional 8 subjects with follicular lymphoma), 76% had grade 3 adverse events (AE). 60% of patients had grade 3 hematologic AEs, including neutropenia (52%) and thrombocytopenia (32%), compared to 32% non-hematologic. The most common immune-related AEs were hypothyroidism (n=3, 12%), hepatitis (n=3, 12%) and pneumonitis (n=2, 8%). Four patients who experienced serious AEs due to pericarditis (n=2), hemophagocytic lymphohistiocytosis, and bullous dermatitis were taken off study. ENT was dose-reduced in 8 patients and was temporarily held without dose-reduction in 11 patients.


The combination of PEM and ENT is tolerable and induces high response rates in R/R HL, some of which appear durable, including in patients who have previously progressed on anti-PD-1 blockade.

Disclosures: von Keudell: Merck: Consultancy, Honoraria. Vardhana: Other: Other: SAV has received honoraria from Agios Pharmaceuticals and Rheos Pharmaceuticals, is an advisor for Immunai and has consulted for ADC Therapeutics. Moskowitz: Incyte: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Research Funding; Imbrium Therapeutics, L.P.: Consultancy; Miragen Therapeutics: Consultancy; Seattle Genetics: Consultancy; Merck: Consultancy. Kumar: Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; AbbVie: Research Funding; Adaptive Biotechnologies,: Research Funding; Celgene: Research Funding; Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board; Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board; Celgene: Honoraria, Other: Honoraria for Advisory Board. Batlevi: Life Sci, GLG, Juno/Celgene, Seattle Genetics, Kite: Consultancy; Janssen, Novartis, Epizyme, Xynomics, Bayer, Autolus, Roche/Genentech: Research Funding. Matasar: Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Immunovaccine Technologies: Honoraria, Research Funding; IGM Biosciences: Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Rocket Medical: Consultancy, Research Funding; Teva: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy; Bayer: Consultancy, Honoraria, Research Funding; Merck: Consultancy; Genentech, Inc.: Consultancy, Honoraria, Research Funding. Horwitz: Kyowa Hakka Kirin: Consultancy, Research Funding; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Forty Seven: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Portola: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Kura Oncology: Consultancy; Miragen: Consultancy; Myeloid Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; ASTEX: Consultancy; Celgene: Consultancy, Research Funding. Dogan: National Cancer Institute: Research Funding; AbbVie: Consultancy; EUSA Pharma: Consultancy; Takeda: Consultancy; Seattle Genetics: Consultancy; Corvus Pharmaceuticals: Consultancy; Physicians Education Resource: Consultancy; Roche: Consultancy, Research Funding. Younes: Takeda: Consultancy; Novartis: Consultancy; AstraZeneca: Current Employment; BMS: Consultancy; Janssen: Consultancy; BioPath: Consultancy; Curis: Consultancy; Daiichi Sankyo: Consultancy; HCM: Consultancy; Epizyme: Consultancy. Joffe: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH