4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company focused on autoimmune and cancer indications, announces the presentation of Phase II data from Hodgkin Lymphoma patients treated in the 1st Simon Stage cohort of the ongoing SAPHIRE study with resminostat (4SC-201), an oral pan-histone deacetylase (HDAC) inhibitor, at the 8th International Symposium on Hodgkin Lymphoma in Cologne, Germany.
The oral presentation will be given by the lead investigator of the SAPHIRE study, Prof Dr Jan Walewski of the Marie-Skłodowska-Curie Memorial Institute in Warsaw, Poland. It highlights initial safety and tolerability as well as efficacy data from the first 18 patients with relapsed or refractory Hodgkin Lymphoma in this study.
Daily oral application of 600 mg resminostat for 5 consecutive days per 2-week treatment cycle was well tolerated with the majority being mild to moderate gastrointestinal and haematological side effects. In addition, a number of anaemia cases were observed, however these were judged as being primarily related to the underlying disease. Pharmacokinetic data indicate good bioavailability of this HDAC inhibitor and plasma exposure levels yielded significant pharmacodynamic activity as exemplified by time dependent HDAC enzyme inhibition after dosing.
In this first patient cohort, the average treatment duration with resminostat reached approximately nine weeks. Anti-tumour activity of the drug was assessed every six weeks by combination of computer tomography (CT) and positron-emission tomography (PET), a technique which allows the simultaneous evaluation of changes in the metabolic activity and the size of a tumour lesion. Based on established PET/CT evaluation criteria, 10 patients out of 18 benefited from treatment with resminostat with two patients being assessed as partial responders (PR) (i.e. more than 50% reduction in size of tumour lesions) and a further eight patients with stabilization of disease (SD). Based on PET analysis almost all of these patients showed a diminished metabolic activity of their lesions with the majority being evaluated as partial metabolic responders (more than 25% decrease in PET activity). These results are based on intermediate analysis of the data and are therefore subject to final review.
According to the statistical design of the SAPHIRE study (Simon two-stage design), a minimum number of five responders were required in this reported 1st Simon stage in order to extend the study to a second enrolment phase of an additional 15 patients (the 2nd Simon stage). After reaching this threshold the study has recently proceeded into the 2nd Simon stage recruitment phase. Due to the good tolerability and side effect profile observed in this relatively young HL patient population an optional increase of the daily dose of resminostat from 600 mg to 800 mg has been implemented.
Prof Walewski of the Marie-Skłodowska-Curie Memorial Institute in Warsaw, Poland, the lead investigator of the SAPHIRE study, commented: 'Despite the fact that patients with Hodgkin Lymphoma often respond well to first-line treatment with chemotherapy, there is an urgent medical need for new therapeutic approaches for patients relapsing or becoming refractory to standard therapy. For patients not responding to second line high-dose chemotherapy the 5-year progression-free survival rate is as low as 17%. Hodgkin Lymphoma patients are often very young and the repeated use of chemotherapy can lead to secondary tumour developments in addition to the primary lymphatic cancer. Based on the initial data presented on the 1st Simon stage of the trial, we are hopeful that resminostat may provide a new therapy option to relapsed or refractory HL patients.'
Dr Bernd Hentsch, Chief Development Officer at 4SC, commented: 'We were very pleased with these initial results and are hopeful of the potential of our oral, pan-HDAC Inhibitor resminostat as a monotherapy treatment for advanced Hodgkin Lymphoma patients. We feel that this indication could provide a clinical proof-of-concept for resminostat, which is currently also being evaluated as a combination treatment in solid tumour indications.'
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