Abexinostat in Patients with NHL and CLL: Results of an Ongoing Phase 2 Study
Abexinostat is an orally available histone deacetylase (HDAC) inhibitor that differs from the approved HDAC inhibitors vorinostat, romidepsin, and belinostat by its pharmacokinetic profile and oral dosing schedule. In previous phase 1 clinical evaluations, abexinostat showed a manageable toxicity profile and durable responses in patients with relapsed/refractory follicular lymphoma (FL). Ribrag and colleagues reported results of A phase 2 study evaluated abexinostat monotherapy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL); Ribrag and colleagues reported results of relating to the NHL subgroup.1,2
In this phase 2 trial, eligible patients received oral abexinostat at the recommended 80 mg twice daily for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity; the primary end point was overall response rate (ORR). A total of 100 patients were enrolled, including 16 with CLL, 17 with diffuse large B-cell lymphoma (DLBCL), 18 with FL, 16 with mantle-cell lymphoma, 18 with T-cell lymphoma (T-CL), and 15 with marginal zone lymphoma or other NHL subtypes. Overall, 55% of patients discontinued study treatment due to progressive disease and 25% due to adverse events (AEs). Among the 87 patients evaluable for efficacy, an ORR of 28% was achieved, including a 5% complete response (CR) rate. By NHL histology, ORRs of 56%, 40%, and 31% were achieved in the FL, T-CL, and DLBCL subtypes, respectively, with median durations of response (DOR) of 26.0 weeks, 32.1 weeks, and 8.1 weeks, respectively. Grade ?3 AEs were reported in 86% of patients; grade ?3 treatment-emergent AEs were thrombocytopenia (80%), neutropenia (28%), and anemia (22%). Serious AEs were reported in 46% of patients, and included thrombocytopenia (15%), anemia (7%), and pneumonia (6%); Class effect gastrointestinal toxicities were experienced by less than 5% of patients. Treatment discontinuations due to AEs were mainly due to hematologic toxicities such as thrombocytopenia (n=9) and neutropenia (n=5). Based on these study results, the authors concluded that abexinostat monotherapy was associated with promising efficacy and a manageable toxicity profile in patients with NHL that was similar to those of other HDAC inhibitors.
- Morschhauser F, et al. Invest New Drugs. 2015;33(2):423-431.
- Ribrag V, et al. ASH 2015. Abstract 256.