Efficacy and safety of ifupinostat in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase 2 study.

Ifupinostat (BEBT-908) is a novel dual-targeted inhibitor of histone deacetylase (HDACs) and phosphatidylinositol 3-kinase alpha (PI3Kα). We evaluated the efficacy and safety of ifupinostat monotherapy in patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. Eligible participants received intravenous ifupinostat at 22.5 mg/m² on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. From June 2020 to July 2022, 128 patients were enrolled and included in the safety set (SS), and 115 patients were in the efficacy analysis set (EAS). At the data cutoff (July 2023), the median follow-up was 19.58 months (95% confidence interval [CI] 16.82-21.95). The ORR was 36.5% (42/115, 95% CI 27.7-46.0), with a complete response rate of 11.3% (13/115). The median DoR was 6.2 months (95% CI 3.5-14.5), median PFS was 2.7 months (95% CI 1.6-3.7), and median OS was 9.9 months (95% CI 7.8-14.8). Treatment-related adverse events (TRAEs) occurred in 99.2% (127/128) of patients, and ≥grade 3 TRAEs in 86.7% (111/128). The most common ≥grade 3 TRAEs were thrombocytopenia (75.8%, 97/128), neutropenia (33.6%, 43/128), and leukopenia (22.7%, 29/128). No treatment-related deaths occurred. Ifupinostat demonstrated promising efficacy and a manageable safety profile as a new therapeutic alternative for patients with r/r DLBCL. Clinical Trial Registry Number: ChiCTR1900028179.