Safety, pharmacokinetics, and efficacy of abexinostat, an novel histone deacetylase inhibitor, in Chinese patients with relapsed/refractory B cell non-Hodgkin lymphoma: a Phase 1 study

作者：Lin Gui, Zucheng Xie, Yan Qin, Peng Liu, Jianliang Yang, Xinrui Chen, Zhenyu Li, Ran Tao, Yuankai Shi · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-14370-y · 被引用次数：4 · 研究领域：Histone Deacetylase Inhibitors Research、Acute Myeloid Leukemia Research、Lymphoma Diagnosis and Treatment

Abexinostat, an novel pan-histone deacetylase inhibitor, induces tumor apoptosis and demonstrates therapeutic potential in B cell non-Hodgkin lymphoma (NHL). This phase 1 study investigate the safety, pharmacokinetics (PK), and efficacy of abexinostat in Chinese patients with relapsed/refractory (r/r) B cell NHL. Patients with r/r B cell NHL received abexinostat orally at escalating doses of 40 mg twice daily (bis in die, BID), 60 mg BID, and 80 mg BID with a 4-h interval, for seven days followed by a 7-day drug-free interval. Patients took abexinostat once on 3 days before day 1 (D-3) of the first cycle in single dose period. If no dose limiting toxicity (DLT) occurred from D-3 to C1D1, the continuous dose period was started from C1D1, abexinostat was given BID. The Primary endpoints were safety and PK. From April 13, 2020 to November 30, 2023, 12 r/r B cell NHL patients were enrolled, including 6 follicular lymphoma (FL), 5 diffuse large B cell lymphoma (DLBCL) and 1 mantle cell lymphoma (MCL). 11 patients received at least one dose abexinostat included in the safety set. No DLT were observed, 80 mg BID was the recommended phase 2 dose (RP2D). Most treatment emergent adverse events (TEAEs) were grade 1 or 2, and grade 3 TEAEs included thrombocytopenia (2/11, 18.2%) and hypertriglyceridemia (3/11, 27.3%). The median time to maximum concentration (T max ) was 0.5–1.0 h and the median terminal elimination half-life (T 1/2 ) was 2.56–8.31 h. Ten patients were included in full a...