Resminostat In Relapsed or Refractory Hodgkin Lymphoma: Initial Results of the SAPHIRE Phase II Trial with a Novel Oral Histone Deacetylase (HDAC) Inhibitor.

Abstract 2811

Resminostat (4SC-201) is a novel pan-HDAC inhibitor that has shown anti-tumor activity in a broad panel of preclinical models and revealed a very favorable safety and promising efficacy profile in patients with various solid tumor types in an initial Phase I trial. Resminostat is currently under investigation in a number of Phase II clinical trials. The SAPHIRE study evaluates the therapeutic activity of resminostat in relapsed/refractory Hodgkin Lymphoma (HL) patients after high dose chemotherapy and autologous hematopoietic stem cell transplantation. The trial is designed as an open-label, single-arm international trial with a Simon Minimax design. Resminostat is administered orally at a once daily dose of 600 mg in 2-week cycles consisting of 5 consecutive days treatment followed by a 9 day treatment free period. Dose delay and reduction is allowed for management of adverse events. Patients undergo assessment of disease status by computed tomography in combination with positron emission tomography (PET/CT), as recommended by the International Working Group (IWG) criteria for the evaluation of HL. PET/CT scans are conducted after cycle 3 and cycle 6 and thereafter every 4th cycle during an optional follow-up treatment period in which patients may remain on treatment until disease progression or occurrence of intolerance to protocol therapy. The primary endpoint of the study is the estimation of overall objective response rate (OOR), secondary endpoints include time to response (TTR), duration of response (DOR), safety and tolerability and the study of drug regulated biomarkers in this patient cohort. As of July 2010, 19 patients with advanced HL have been enrolled in the 1st Simon stage of the study. Treatment was well tolerated with common related grade 2 –3 AEs being anemia and thrombocytopenia that were well manageable by dose modification or symptomatic treatment. Analysis of PET/CT data through an independent central assessment committee confirmed the achievement of the clinical activity requirements for the advancement of the trial into the 2nd Simon recruitment phase. Updated clinical data of this ongoing study on the efficacy and safety of the HDAC inhibitor resminostat in relapsed/refractory HL patients will be presented at the meeting.