{ "abstract": "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.", "abstract_shown": true, "affiliations": [ "Department of Medical Oncology, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation of Innovative Drugs for Major Diseases, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China. syuankai@cicams.ac.cn.", "Department of Medical Oncology, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation of Innovative Drugs for Major Diseases, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.", "Hematology Department, Henan Cancer Hospital, Henan, PR China.", "Lymphoma Department, Guangdong Provincial People's Hospital, Guangdong, PR China.", "Lymphoma Hematology Department, Hunan Cancer Hospital, Hunan, PR China.", "Lymphoma and Head and Neck Tumor Department, Fujian Cancer Hospital, Fujian, PR China.", "Hematology Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, PR China.", "Hematology Department, Hebei Cancer Hospital, Hebei, PR China.", "Oncology Department, Jilin Cancer Hospital, Jilin, PR China.", "Internal Medicine Department, Linyi Cancer Hospital, Shandong, PR China.", "Lymphoma Department, Zhejiang Cancer Hospital, Zhejiang, PR China.", "Hematology Department, The Affiliated Hospital of Qingdao University, Shandong, PR China.", "Oncology Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China.", "Hematology Department, The First Hospital of Jilin University, Jilin, PR China.", "Hematology Department, The First Affiliated Hospital of Nanchang University, Jiangxi, PR China.", "Oncology Department, Fudan University Shanghai Cancer Center, Shanghai, PR China.", "Lymphoma Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, PR China.", "Hematology Department, Shandong Provincial Qianfoshan Hospital, Shandong, PR China.", "Oncology Department, Changsha Kexin Cancer Hospital, Hunan, PR China.", "Oncology Department, The Second Xiangya Hospital of Central South University, Hunan, PR China.", "Hematology Department, Xiangya Hospital of Central South University, Hunan, PR China.", "Lymphoma Department, Tianjin Medical University Cancer Institute & Hospital, Tianjin, PR China.", "Oncology Department, The Second Hospital of DaLian Medical University, Liaoning, PR China.", "Oncology Department, The First Affiliated Hospital of Zhengzhou University, Henan, PR China.", "Hematological Oncology Department, Anhui Provincial Cancer Hospital, Anhui, PR China.", "Oncology Department, The Fifth Affiliated Hospital Sun Yat-san University, Guangdong, PR China.", "Radiation Injury Treatment Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, PR China.", "Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, PR China.", "BeBetter Med Inc., Guangzhou, Guangdong, PR China." ], "article_type": "research article", "arxiv": null, "author_total": 31, "authors": [ { "affs": [ 0 ], "name": "Yuankai Shi", "orcid": "0000-0002-3342-4964" }, { "affs": [ 1 ], "name": "Peng Liu" }, { "affs": [ 2 ], "name": "Yufu Li" }, { "affs": [ 3 ], "name": "Wenyu Li" }, { "affs": [ 4 ], "name": "Hui Zhou" }, { "affs": [ 5 ], "name": "Yu Yang" }, { "affs": [ 6 ], "name": "Jie Jin" }, { "affs": [ 7 ], "name": "Yuhuan Gao" }, { "affs": [ 8 ], "name": "Weijie Xu" }, { "affs": [ 9 ], "name": "Meifang Zheng" }, { "affs": [ 10 ], "name": "Haiyan Yang" }, { "affs": [ 11 ], "name": "Hongwei Xue" }, { "affs": [ 12 ], "name": "Zhigang Peng" }, { "affs": [ 13 ], "name": "Ou Bai" }, { "affs": [ 14 ], "name": "Fei Li" }, { "affs": [ 15 ], "name": "Fangfang Lv" }, { "affs": [ 16 ], "name": "Liling Zhang" }, { "affs": [ 17 ], "name": "Ning Huang" }, { "affs": [ 18 ], "name": "Yi Luo" }, { "affs": [ 19 ], "name": "Chunhong Hu" }, { "affs": [ 20 ], "name": "Yajing Xu" }, { "affs": [ 21 ], "name": "Huilai Zhang" }, { "affs": [ 22 ], "name": "Xiuhua Sun" }, { "affs": [ 23 ], "name": "Xin Li" }, { "affs": [ 24 ], "name": "Kaiyang Ding" }, { "affs": [ 25 ], "name": "Linjuan Zeng" }, { "affs": [ 26 ], "name": "Haiyan Zhu" }, { "affs": [ 27, 28 ], "name": "Yajie Cao" }, { "affs": [ 28 ], "name": "Yonglong Yang" }, { "affs": [ 28 ], "name": "Kegang Jiang" }, { "affs": [ 28 ], "name": "Changgeng Qian" } ], "bibtex": "https://research.draconitic.com/paper/fq6w6m5rqv79y.bib", "cited_by": 0, "doi": "10.1038/s41392-026-02926-8", "fulltext_url": "https://europepmc.org/articles/PMC13677673", "id": "fq6w6m5rqv79y", "issns": [ "2095-9907", "2059-3635" ], "landing_url": "https://europepmc.org/article/MED/42893991", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "QH301-705.5" ], [ "lcc", "R" ], [ "openalex", "2734|Lymphoma Diagnosis and Treatment" ] ], "openalex": "W7222886711", "pdf_url": "https://europepmc.org/articles/PMC13677673?pdf=render", "pmcid": "PMC13677673", "pmid": "42893991", "published": "2026-10-19", "publisher": "Nature Publishing Group", "ris": "https://research.draconitic.com/paper/fq6w6m5rqv79y.ris", "sources": [ { "first_seen": "2026-10-30T12:19:33Z", "native_id": "MED:42893991", "source": "europepmc", "url": "https://europepmc.org/article/MED/42893991" }, { "first_seen": "2026-10-30T13:46:34Z", "native_id": "74b0376016fe480fb20758d7ca47f451", "source": "doaj", "url": "https://doi.org/10.1038/s41392-026-02926-8" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2734|Lymphoma Diagnosis and Treatment", "subfield": "general" } ], "title": "Efficacy and safety of ifupinostat in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase 2 study.", "title_text": "Efficacy and safety of ifupinostat in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase 2 study.", "type": "peer-reviewed", "updated_at": "2026-10-30T13:46:34Z", "url": "https://research.draconitic.com/paper/fq6w6m5rqv79y", "venue": "Signal transduction and targeted therapy", "versions": [] }