15ICML 279--P Prior radiation Prior brentuximab Prior HDAC inhibitor Prior PD-1 antibody Prior transplant Refractory disease Number of prior therapies Extranodal disease Number of nodal sites Bulky disease Total number Hodgkin lymphoma cohort Prior radiation Prior R-CHOP Prior transplant Refractory disease Number of prior therapies Extranodal disease Number of nodal sites Bulky disease Total number cohort Female Male >65 years old Age Total Number References References enrollment Table at 1. Patient characteristics Results Results as long as there was clinical benefit and not the most recent therapy therapy recent most the not and benefit clinical was there as long as ! Key inclusion criteria Patient population: 2) instage cohort per 1, patients 18 instage cohort per (21patients ! ! ! designStudy 12 11 10 9 8 7 6 5 4 3 2 1 Pasqualucci, Ogura, Batlevi, Oki, Jiang, Woods, Woods, Ribrag, Younes, Batlevi, Chen, Prior treatment with HDAC inhibitor or anti-PD1 antibody allowed allowed oranti-PD1inhibitorHDAC antibody with Prior treatment cohorts inboth subjects total 78 minimax design: Simon2 stage 2 cohorts:FLHL and institution single II, arm,label, Phase open single Lesokhin, Younes, Background achieving disease control for >6 months >6 for control disease achieving 24% with patients of in50% benefit clinical demonstrated (HL) and lymphoma Hodgkin with in49patients ! inmice models invarious tumor anti-PD-1 antibodies with combined when synergistically act and Tlymphocytes, incirculating PD-1 expression downregulate cells, lymphoma inBcell recognition immune antigen-specific restore ! (FL) lymphoma follicular of 40% including malignancies, CREBBP,inlymphoid EP300)common are ! II (MHC) promoters complex majorand histocompatibility genes suppressor tumor of ! malignancies hematologic inmost 1)tumorigenesis drive (Figure ! Methods Blood Cancer Journal. Blood Cancer The phase II ENGAGE-501 trial investigated single agent agent single investigated trial II ENGAGE-501 phase The to shown been have inhibitors (HDAC) deacetylase Histone (e.g. genes acetyltransferase histone of Inactivating mutations sites at chromatinstate inanopen results acetylation Histone modifications histone including dysregulation Epigenetic CancerDiscovery. J Clin Oncol. Oncol. Clin J Br J Haematology. JHaematology. Br Haematologica. Haematologica. Haematologica. Haematologica. Can Immunol Res. Br J Haematology. JHaematology. Br J Clin Oncology. Oncology. Clin J Lancet Oncology. Oncology. Lancet J Clin Oncol. Oncol. Clin J Nature. Epidemiology and Biostatistics and Epidemiology 1 Yahalom David Sermer Memorial Sloan-Kettering Cancer Center, Cancer Sloan-Kettering Memorial New York, NY, USA; David Sermer NOVEL TREATMENTS 35,2125-2132,2017

47,189-95, 2011 Relapsed and/or refractory HL and FL and HL refractory and/or Relapsed

34,2698-2704,2016) 102,903-909,2017 101,2016 968-975, 30,2197-03,2012 7, 38-53,7, 2017 6 (50%) 6 (50%) 4 (33%) Range 26-81, median 60 12 3 (60%) 5 (100%) 1 (20%) 1 (20%) 1 (20%) 3 (60%) Range 2-11, median 3 3 (60%) Range 1-5, median 3 2 (40%) 5 1 (14%) 6 (86%) 0 1 (14%) Range 2-4, median 3 4 (57%) Range 2-8, median 5 1 (14%) 7 1,3 165,768-776,2014 3,2015 1375-85, 17,1283-1294,2016 4, e236, 2014. 178,434-441,2017 , JurgenRademaker 1,2 , Santosha Vardhana 2-4

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1,4 inhibitor as monotherapy * Patient previously inhibitor with HDAC treated and PD-1 – complete responseCR – minorMR response; – partial PR response – progressivePD disease; SD – stable disease; Purple bars – FL; Blue Bars – HL Figure 4. Duration on(days) treatment , Dogan Ahmet criteria (% change) incriteria 11 evaluable patients Figure by tumorRECIL 3. responses Best in relapsed and refractory Hodgkinin andrelapsed lymphoma refractory and follicular lymphoma anddata from a phase II Safety early trial of pembrolizumab and entinostat 1,2 Stopped due diseaseto progression Stopped for consolidation therapy (radiation, allogeneic transplant) Stopped due toxicityto (pericarditis, HLH, bullous dermatitis) Continues on study , Connie Batlevi infectious pneumonitis pneumonitis infectious ! drug study of days 7 within medications orimmunosuppressive equivalent) prednisone ! ! Key exclusion criteria medications ! ! ! History of non-infectious pneumonitis requiring steroids, interstitial lung disease, active non- active disease, lung interstitial requiringsteroids, pneumonitis non-infectious of History daily 10 (> mg corticosteroids requiringsystemic orconditions disease autoimmune Active lymphoma of involvement CNS Known suppressive immune all GVHD off andactive no if allowed transplant cell stem Prior allogeneic (FL) (HL) transplant or3priorregimens cell stem autologous for ineligible and 2 priorregimens 0-1 of ECOG Repression suppressor genes cycle arrest,andtumor differentiation, cell Silencing ofB-cell 1,5 , Venkatraman Seshan PRMT5 CH H3R8 3 1,2 , Hamilton Audrey 2 CH H3K18 Department of Medicine; of Medicine; Department SUZ12 3 CO H3K27 EZH2 CH EED 3 * HDAC Complex 1,6 PRC2 , Anas Younes 1,2 , Allison Moskowitz

HAT common epigenetic enzymes common epigenetic enzymes Figure of1. Mechanisms action of

3 DOI: 10.3252/pso.eu.15ICML.2019 Department of Radiation Oncology; Oncology; of Radiation Department DNA damageresponse tumor suppressors, differentiation, Lymphocyte CH H3K18 1,2 3 CO 1,2 Anorexia – 1 Bloating/abdominal pain – 1 ALT elevation – 1 Headache – 1 Hyperbilirubinemia – 1 Pleural effusion – 1 Hypothyroid – 1 Pericarditis – 1 Fever – 1 Dysgeusia – 2 Musculoskeletal pain – 2 Febrile neutropenia – 1 Rash – 2 (17%) Nausea/vomiting – 2 (17%) Mucositis – 3 (25%) Fatigue – 5 (42%) Anemia – 5 (42%) Neutropenia – 7 (58%) Thrombocytopenia – 7 (58%) Total Non-hematologic – 11 (92%) Total Hematologic – 9 (75%) Total – 12 (100%) All grade AEs , Philip Caron Table 2. Toxicities Brentuximab vedotinBrentuximab with year-old female 71 Hodgkin to lymphoma, refractory ICE,ABVD, and Figure 5. Fused PET/CT documentingonin 9 weeks treatment a after CR PTEFb H3K18 CH BRD4 Conclusions Oncogene expression 3 CO Pol II Superenhancer efficacious in the study population, especially in Hodgkin lymphoma Early results suggest the combination that is and ofENT PEM both safe and 1,2 , Craig Moskowitz Expression Poster 4

Department of Radiology; of Radiology; Department

presented Febrile neutropenia – 1 Rash – 1 Anemia – 2 (17%) Neutropenia – 6 (50%) Thrombocytopenia – 3 (25%) Total Non-hematologic – 1 (8%) Total Hematologic – 7 (58%) Total - 8 (67%) Grade 3 or 4 AEs microenvironment tumor the and blood biomarkers inperipheral immune ! survival (PFS) progression-free ! relapsed and refractory (R/R) HL and FL. antibody pembrolizumab in (PEM) patients with inhibitor entinostat and (ENT) the PD1-blocking phase II trial investigating the combination of the HDAC ! 1CR 40%, including FL was ! (ORR) rate response overall 66-69% a demonstrate II that trials phase on HL based classical refractory relapsed/ for approved FDA are nivolumabpembrolizumab and ! patients (FL)HL and lymphoma infollicular 56% 11.5%rangingfrom to responses demonstrated have abexinostat and , ! Primary Objectives describe We early safety and efficacy data from a including anti-PD1 antibodies, with blockade Checkpoint ,, inhibitors,HDAC including Other at: 1,2 In a phase 1 study of nivolumab, the ORR in 10 patients with with ORRnivolumab, in10 patients of the 1study Inphase a Exploratory Objectives: , Matthew Matasar Figure plan2. andStudy treatment schema Printing 6-9 supported 5 Department of Pathology; of Pathology; Department by : To evaluate ORR 12and :month Toevaluate : 1,2 12 , Erin Biggar tumor biopsies sequencing (NGS) from results Table 3. Next-generation To correlate outcomes with various with outcomes Tocorrelate Blue Blue – HL; Purple – FL 12 11 10 9 8 7 6 5 4 3 2 1 Patient 10-11 WHSC1 MLL2, SETD1B, Arid1A, CREBBP, MLL2 Not done MLL2 CREBBP, EZH2, MLL2 Arid1B, CREBBP, Arid1A TET1 CREBBP, MLL2, Not done Not done MLL2 SETDB/7 EP300, MLL2, KDM5C, ARID1A, Not done alterations Mutations/ Epigenetic 1,2 , Echo Leung 6 Department of Department

PD PR PR SD Not evaluable MR PD MR CR SD PR PR Best Response 1,2 , Joachim