title: ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma.
abstract: Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor. Forty-nine patients were enrolled: 33 patients on Schedule A (10 or 15 mg oral entinostat once every other week); 16 patients on Schedule B (15 mg oral entinostat once weekly in 3 of 4 weeks). Patients received a median of 3 prior treatments (range 1-10), with 80% of the patients receiving a prior stem cell transplant and 8% of patients receiving prior brentuximab vedotin. In the intention-to-treat analysis, the overall response rate was 12% while the disease control rate (complete response, partial response, and stable disease beyond 6 months) was 24%. Seven patients did not complete the first cycle due to progression of disease. Tumor reduction was observed in 24 of 38 (58%) evaluable patients. Median progression-free survival and overall survival was 5.5 and 25.1 months, respectively. The most frequent grade 3 or 4 adverse events were thrombocytopenia (63%), anemia (47%), neutropenia (41%), leukopenia (10%), hypokalemia (8%), and hypophosphatemia (6%). Twenty-five (51%) patients required dose reductions or delays. Pericarditis/pericardial effusion occurred in one patient after 12 cycles of therapy. Future studies are warranted to identify predictive biomarkers for treatment response and to develop mechanism-based combination strategies. (clinicaltrials.gov identifier: 00866333).
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Connie Lee
authors.initials: CL
authors.lastname: Batlevi
authors.affiliation: John Hopkins University, Baltimore, MD, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Kasamon
authors.affiliation: University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: R Gregory
authors.initials: RG
authors.lastname: Bociek
authors.affiliation: Tower Cancer Research Foundation, Beverly Hills, CA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.affiliation: University of Colorado Cancer Center, Aurora, CO, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Copeland
authors.affiliation: Syndax Pharmaceuticals, Inc., Waltham, MA, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sorensen
authors.affiliation: Syndax Pharmaceuticals, Inc., Waltham, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ordentlich
authors.affiliation: Syndax Pharmaceuticals, Inc., Waltham, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Cruickshank
authors.affiliation: Syndax Pharmaceuticals, Inc., Waltham, MA, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Kunkel
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Buglio
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernandez-Ilizaliturri
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA MD Anderson Cancer Center, Houston, TX, USA younesa@mskcc.org.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006689:Hodgkin Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat