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1763 Mocetinostat (MGCD0103), An Isotype-Selective Histone Deacetylase (HDAC) Inhibitor, Produces Clinical Responses In Relapsed/Refractory Hodgkin Lymphoma (HL): Update From a Phase II Clinical Study

Program: Oral and Poster Abstracts
Session: Lymphoma - Chemotherapy, excluding Pre-Clinical Models: Poster I
Saturday, December 4, 2010, 5:30 PM-7:30 PM
Hall A3/A4 (Orange County Convention Center)
Poster Board I-743

Anas Younes1, R. Gregory Bociek2, John Kuruvilla3*, Pierre Laneuville, MD4, Henry C. Fung5, Michel Drouin6*, Tracy Patterson6*, Jeffrey Besterman6* and Robert E. Martell7

1M.D. Anderson Cancer Center, Houston, TX
2Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
3University of Toronto, Princess Margaret Hospital, Toronto, QC, Canada
4Division of Haematology, McGill University Health Center, Montreal, QC, Canada
5Rush University Medical Center, Chicago, IL
6MethylGene Inc., Montreal, QC, Canada
7Cancer Center, Tufts Medical Center, Boston, MA

Background: HL patients with relapsed or refractory disease are incurable with standard therapies and new options are needed. Deregulation of HDAC activity can cause malignant diseases in humans. Mocetinostat inhibits Class I and IV HDACs and was shown to have preclinical and clinical activity. Methods: This was an open-label, Phase II trial in adults (≥18 years old) with relapsed/refractory HL. Patients initially received MGCD0103 at a starting dose of 110 mg (110 mg cohort) or 85 mg (85 mg cohort) 3x per week in 4-week cycles. Eligibility criteria included ≥1 target lesion (≥2 cm), no limit of prior therapies, ECOG status of 0–1, and platelet counts ≥25,000/μL. Tumor responses were determined every 8 weeks. The primary objective of this study was to estimate the treatment success rate defined as complete response (CR) + partial response (PR) + durable stable disease (SD for at least 6 cycles). Results: A total of 51 patients (23 patients in the 110 mg cohort and 28 patients in the 85 mg cohort) were enrolled (median age: 33 years old, range: 19-68 years old; gender: 29 male, 22 female; 84% caucasians; ECOG:  0: 49%, 1: 51%). Two patients experienced CR (110 mg cohort), 12 patients experienced PR (6 patients in each cohort) and 1 patient experienced durable SD (in the 85 mg cohort). The success rate was found to be 35% in the efficacy evaluable population (n=43) and 29% in the intent-to-treat population (n=51). Treatment-related adverse events of grade 3 or higher in ≥ 5% of patients included: thrombocytopenia (22%), fatigue (16%), neutropenia (14%), pneumonia (12%), anemia (10%), pericardial effusion (6%) and abnormal liver function tests (6%). Conclusions: Mocetinostat demonstrated single agent activity in heavily pretreated relapsed/refractory HL patients. The response rate reported in this study is among the best single agent activity described in HL with HDAC inhibitors, especially in the context of the minimal hematological toxicity observed. Despite the modest increased incidence of non-fatal pericardial effusions, the benefits of Mocetinostat outweigh the risks in this heavily pretreated patient population for which no curative options are available.  Further development of Mocetinostat in HL is warranted, especially in less heavily treated patients and with prospective cardiac evaluations.

Disclosures: Younes: SBIO: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Seattle Genetics: Honoraria, Research Funding. Kuruvilla: Otsuka: Honoraria; Amgen: Honoraria; Celgene: Research Funding; Hoffman Laroche: Honoraria, Research Funding; Genzyme: Honoraria. Drouin: Methylgene: Employment. Patterson: Methylgene: Employment. Besterman: Methylgene: Employment, Equity Ownership. Martell: Methylgene: Equity Ownership.

*signifies non-member of ASH