Abexinostat, a histone deacetylases inhibitor, for patients with relapsed or refractory follicular lymphoma: a multi-center, single-arm phase 2 study

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: ORR 69.5% with complete response rate 14.6%

• Primary Outcome: Objective response rate: 69.5% (57/82 patients)

• Nnt Or Sensitivity: Disease control rate 91.5% (95% CI 83.2-96.5%); median PFS 13.80 months

• Confidence Interval: 95% CI 58.4-79.2% for ORR

Clinical Application

Oral administration with manageable toxicity profile, though requires careful hematologic monitoring for cytopenias Would require TGA approval and PBS listing. May fill unmet need for third-line FL treatment, complementing existing options like lenalidomide and CAR-T therapy available through specialized centers Heavily pre-treated relapsed/refractory follicular lymphoma patients who have failed at least two prior systemic therapies

Abstract

This phase 2, single-arm, multi-center study (NCT03934567) evaluates the efficacy and safety of abexinostat, a histone deacetylase inhibitor, in patients with relapsed or refractory (r/r) follicular lymphoma (FL). Eligible participants had previously received a minimum of two systemic treatment lines, such as cytotoxic agents and/or anti-CD20 monoclonal antibodies. Participants received abexinostat 80 mg oral twice daily on a schedule of seven days on and seven days off, within 28-day cycles, continuing until unacceptable toxicity or disease progression occurred. The primary endpoint was objective response rate (ORR), evaluated by an independent review committee (IRC). Secondary endpoints comprised duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Between May 2, 2019, and November 19, 2023, 90 patients were enrolled. As of October 08, 2024, with a median follow-up of 30.55 months (95% confidence interval [CI] 23.72-33.64), 17.8% (16/90) of patients were still on study treatment. The ORR was 69.5% (57/82, 95% CI 58.4-79.2), with a complete response rate of 14.6% (12/82). The DCR was 91.5% (75/82, 95% CI 83.2-96.5). Tumor size reduced in 89% (73/82) of patients. The median DoR was 13.96 months (95% CI 9.20-not reached [NR]) and the median PFS was 13.80 months (95% CI 9.69-30.26). The median OS was 47.18 months (95% CI 45.70-NR). The most common treatment-emergent adverse events were thrombocytopenia (77/90, 85.6%), neutropenia (53/90, 58.9%), and leukopenia (47/90, 52.2%). The results of this study demonstrated that abexinostat had promising efficacy and manageable safety profile, supporting abexinostat as a new treatment option for the third-line or later-line treatment of r/r FL.

References

1. 1.Gui, L., Liu, H., Wang, H., Cao, J., Li, Y., Yu, Y., Gao, Y., Li, Z., Shen, J., Zhang, L., Zhang, Q., Pan, H., Zheng, M., Ke, X., He, H., Guo, S., Wang, Y., Xu, X., Zou, L., Wu, W., & Shi, Y. (2026). Abexinostat, a histone deacetylases inhibitor, for patients with relapsed or refractory follicular lymphoma: a multi-center, single-arm phase 2 study. Signal Transduction and Targeted Therapy. https://doi.org/10.1200/JCO.2013.54.8800