SAN DIEGO, CA—At the 53rd American Society of Hematology Annual Meeting and Exposition, study investigators presented data from the SAPHIRE trial demonstrating that resminostat, an oral pan-histone deacetylase (HDAC) inhibitor, showed considerable anti-tumor activity in a heavily pre-treated population with Hodgkin’s Lymphoma.
SAPHIRE, a Phase 2, open-label, single-arm, international study, enrolled patients who had relapsed or progressed after prior therapy (including high-dose chemotherapy and autologous stem cell transplantation [ASCT]) or were refractory to treatment. The study consisted of two recruitment stages. As of June 2011, 37 patients were enrolled at five study sites. Mean age was 34 years (range 19–71). Twenty-one patients (57%) had ASCT; 14 of those relapsed within one year after ASCT. Twenty-six patients (70%) had ≥5 prior sequences of therapy, with a median of six prior regimens (range 1–12). Stage of disease according to Ann Arbor classification at baseline was: six patients with Stage 2, four patients with Stage 3, and 27 patients with Stage 4.
Resminostat was given at a dose of 600mg orally once daily during the first recruitment stage and at a dose of 800mg orally once daily in the second stage. Patients were treated in 14-day cycles of five consecutive days followed by a nine-day treatment-free period (5+9 schedule). Disease assessment was measured by computed tomography in combination with positron emission tomography (CT/PET) after Cycle 3 and Cycle 6. During an optional extension phase of the study, in which patients continued on resminostat treatment until disease progression, CT/PET was taken every fourth cycle.
The primary endpoint was overall objective response rate (ORR) based on the best response during treatment, classified as complete response (CR) or partial response (PR) following the Revised Response Criteria for Malignant Lymphoma or partial metabolic response (PMR) following the European Organisation for Research and Treatment of Cancer criteria.
As of August 2011, 35 patients had ≥1 post-baseline PET/CT tumor assessments, while the other two patients discontinued early due to adverse events. Currently, one of the 35 patients is still on study therapy in an optional extension phase. Thirty-four patients were evaluated for tumor response – 12 patients were responders (ORR = 35.3%). Of these, there was one CR, three PR and seven PMR. Median time to response was three cycles. Seven additional patients achieved stabilization of the disease. In total, 19 patients (55.6%) gained clinical benefit from resminostat monotherapy.
Dosing with both strengths of resminostat was well tolerated. Treatment-associated Grade 2/3 adverse events included anemia and thrombocytopenia, both of which were controlled with dose adjustment.
Resminostat can be safely administered as oral monotherapy up to 800mg once daily in a 5+9 day treatment schedule, concluded lead author Jan Walewski, MD, PhD, of Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland. “Further development of resminostat in Hodgkin’s lymphoma is warranted,” the study authors added at a presentation of their poster.