Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma  

作　　者：Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li 

机构地区：[1]Department of Oncology,Tianjin Union Medical Center of Nankai University,Tianjin 300121,PR China [2]The Institute of Translational Medicine,Tianjin Union Medical Center of Nankai University,Tianjin 300121,PR China [3]Department of Medical Oncology,Jiangsu Cancer Hospital,The Affiliated Cancer Hospital of Nanjing Medical University,Nanjing 210009,PR China [4]Department of Medical Oncology,Henan Cancer Hospital,The Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450003,PR China [5]Department of Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,PR China [6]Department of Hematology,The Affiliated Hospital of Inner Mongolia Medical College,010050 Hohhot,PR China [7]Department of Hematology,Weifang People’s Hospital,The First Affiliated Hospital of Weifang Medical University,261000 Weifang,PR China [8]Department of Lymphoma&Hematology,Hunan Cancer Hospital,The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,410013 Changsha,PR China [9]Department of Hematology,The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital,050011 Shijiazhuang,PR China [10]Department of Lymphoma,Weihai Central Hospital,264400 Weihai,PR China [11]Department of Hematology and Rheumatology,The Affiliated Zhongshan Hospital of Dalian University,116001 Dalian,PR China [12]Department of Hematology,Beijing Luhe Hospital,101199 Beijing,PR China [13]Department of Hematology,The First Affiliated Hospital of Guangzhou Medical University,510120 Guangzhou,PR China [14]Department of Hematology,The First Affiliated Hospital of Hainan Medical College,570102 Haikou,PR China [15]Department of Hematology,The First People’s Hospital of Foshan,528000 Foshan,PR China [16]Department of Hematology,Shanxi Cancer Hospital,030013 Taiyuan,PR China [17]Department of Lymphoma,Senior Department of Hematology,The Fifth Medical Center of Chinese PLA General Hospital,100039 Beijing,PR China [18]Department of Lymphoma and Head and Neck Cancer,Fujian Cancer Hospital,350014

出　　处：《Signal Transduction and Targeted Therapy》2024年第5期2193-2201,共9页信号转导与靶向治疗（英文）

基　　金：This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.(Nanjing,China)and was supported by grants from National Natural Science Foundation of China(Grant Number,81872902,82073917,and 82070206);National Natural Science Foundation of Guangdong Province(Grant Number,2023A1515011525);The Lymphoma Research Fund of China Anti-Cancer Association,and the Sun Yat-sen University Cancer Center Clinical Research 308 Program(Grant Number,2014-fxy-106 and 2016-fxy-079);Tianjin Key Medical Discipline(Specialty)Construction Project(Grant Number,TJYXZDXK-053B).

摘　　要：This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关 键 词：LYMPHOMA assessed initiated 

分 类 号：R733.1[医药卫生—肿瘤]