Efficacy and safety of ifupinostat (BEBT-908) in combination with rituximab for relapsed/refractory diffuse large B-cell lymphoma: Results from an exploratory phase Ib study.
Year: 2025
Type: conference-abstract
Abstract: 7050 Background: Ifupinostat is a dual HDAC/PI3Kα inhibitor designed to target tumor cell signaling networks by simultaneously inhibiting HDAC and PI3Kα, thereby disrupting tumor cell proliferation and inducing apoptosis. A single-arm pivotal trial of Ifupinostat in patients who received at least two lines of systemic therapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) has been completed, with data currently under NDA review by the NMPA. This exploratory trial evaluates Ifupinostat in combination with rituximab as part of a confirmatory phase 3 trial to further assess its efficacy and safety as a second-line treatment for r/r DLBCL (NCT06164327). Methods: This multicenter Phase 1b trial was designed to evaluate the efficacy and safety of Ifupinostat in combination with rituximab (R) with or without standard second-line regimens (R-GemOx or R-ICE). Cohort 3 included 24 r/r DLBCL patients with prior exposure to at least one systemic therapy, all involving anti-CD20 antibody. Among these, 16 patients (66.6%) were primary refractory, 4 patients (16.7%) were refractory to their most recent line of therapy, and 4 patients (16.7%) were relapsed cases. Treatment consisted of Ifupinostat administered intravenously at a dose of 22.5 mg/m² on days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Rituximab was administered intravenously at a dose of 375 mg/m² on day 1 of each cycle. Tumor assessments were conducted following treatment, and efficacy was evaluated according to the Lugano 2014 criteria. Key endpoints included the objective response rate (ORR) and safety. Results: Of the 24 enrolled patients, 21 completed at least one treatment dose and underwent tumor assessment. The ORR was 76.2%, with 10 patients (47.6%) achieving a complete response (CR) and 6 (28.6%) achieving a partial response (PR). The disease control rate (DCR) was 85.7%. Median progression-free survival (PFS) has not yet been reached (>7.7 months). Common grade 3-4 hematological toxicities observed during treatment included thrombocytopenia (34.8%), leukopenia (17.4%), and lymphopenia (13.0%). No unexpected toxicities were observed, and the safety profile was deemed manageable. Conclusions: The study results demonstrate promising efficacy and a manageable safety profile for Ifupinostat in combination with rituximab as a second-line treatment for r/r DLBCL. These findings support further investigation in confirmatory phase 3 trials, which are currently underway. Clinical trial information: NCT06164327 .
Source: Journal of Clinical Oncology
Authors: Peng Liu, Yufu Li, Yajun Li, Fang Zhu, Ying Cheng, Ou Bai, Wenyu Li, Hui Wu, Xinquan Liang, Yongdong Zhang, Hongwei Xue, Zhiming Li, Changgeng Qian, Yuankai Shi
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences, Hunan Cancer Hospital, Henan Cancer Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, Jilin Province Tumor Hospital, First Hospital of Jilin University, Guangdong Provincial People's Hospital, Fujian Provincial Cancer Hospital, Chenzhou First People's Hospital, Affiliated Hospital of Qingdao University, Sun Yat-sen University Cancer Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410819841