4SC AG, has announced positive topline data from its Phase II SAPHIRE trial with resminostat, its oral pan HDAC inhibitor, in patients with relapsed/refractory Hodgkin’s Lymphoma (HL).
Resminostat monotherapy exhibited substantial anti-tumour activity, including complete and partial tumour responses.
Analysis of tumour response assessments revealed that the study achieved its primary endpoint. Furthermore the study verified the drug to be safe and well tolerated in this advanced stage patient population.
In June 2011 the SAPHIRE trial completed patient enrolment. 33 patients have been evaluated for tumour response which, according to the study protocol, represents the targeted number of patients required for efficacy analyses.
Central assessment of patient tumour data by an independent expert review board revealed objective tumour responses in 11 patients, constituting a 33.3% overall response rate (ORR) and thereby successfully achieving the predefined requirements of the primary endpoint of the study.
This ORR of 33.3% together with a clinical benefit recorded in total for 54.5% of the patients (disease control rate) demonstrates the substantial anti-tumour activity of resminostat monotherapy in an advanced and heavily pretreated Hodgkin’s Lymphoma patient population for which there is currently no established standard therapy available.
Prior to study entry, the patients enrolled received a median of 6 treatments consisting of various chemo- and radiation therapies including autologous stem cell transplantation in 57% of the cases.
The clinical activity of resminostat was measured through PET/CT, the combination of positronemission tomography (PET) and computer tomography (CT). Study responders included 1 complete response (CR) and 3 partial responses (PR) according to Cheson criteria.
Furthermore, 7 patients experienced partial metabolic responses (PMR) according to EORTC criteria. An additional 7 patients achieved stabilization of their disease. Thus, in total 18 of 33 patients, representing 54.5% of all patients evaluated for efficacy, received a clinical benefit from resminostat treatment.
Additional two patients are currently continuing on study therapy in the optional follow-up phase, and have therefore not been subject to final response evaluation by the independent review board.
Treatment with resminostat was generally well tolerated with common grade 2-3 adverse events mainly being of gastrointestinal (nausea) or hematological (anemia, thrombocytopenia) origin.
All adverse events were well manageable by dose modification or symptomatic treatment. Assessment of pharmacokinetic (PK) parameters confirmed the favorable profile of the oral administration route and dose dependent resminostat plasma concentrations.
“We are very encouraged by the results from this trial in a very heavily pre-treated patient population. With an overall response rate of 33.3% and with more than half of the patients experiencing a clinical benefit resminostat could become a novel therapy in Hodgkin’s Lymphoma,” said Ulrich Dauer, Chief Executive Officer of 4SC.
Dauer continued, “This excellent efficacy data in patients with no further established treatment options combined with the very positive safety profile of resminostat provides us with the information we need to initiate the next development steps for this compound. We intend to discuss the path towards registration with the regulatory agencies in the near future.”
Final data from this trial, including secondary endpoints, will be presented at an upcoming international scientific conference.