The oral PI3Kδ inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: A phase 2, single-arm, open-label clinical trial
机构：[1]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[2]Tianjin Institutes of Health Science, Tianjin 301600, China[3]Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian 116023, China[4]Department of Lymphoma, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China[5]Department of Lymphoma, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100071, China[6]Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China[7]Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China[8]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China[9]Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[10]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China华中科技大学同济医学院附属同济医院[11]Department of Medical Oncology, Hubei Cancer Hospital, Wuhan 430079, China[12]Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China[13]Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[14]Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China河南省肿瘤医院[15]Department of Lymphoma & Hematology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China[16]Department of Lymphoma and Head and Neck Cancer, Fujian Provincial Cancer Hospital, The Affiliated Tumor Hospital of Fujian Medical University, Fuzhou 350014, China[17]Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen 361003, China[18]Department of Haematology/Oncology and Paediatric Oncology, Guangxi Medical University Affiliated Cancer Hospital, Nanning 530031, China[19]Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China浙江大学医学院附属第一医院[20]Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Chengdu 610051, China四川省肿瘤医院[21]Department of Hematology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China[22]Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang 330008, China[23]Department of Internal Medicine and Oncology, Zhongshan Hospital, Xiamen University, Xiamen 361004, China[24]Department of Hematology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China深圳市中医院深圳医学信息中心[25]Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China南方医科大学珠江医院[26]Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050019, China河北医科大学第四医院[27]Clinical Development Department, Shanghai Yingli Pharmaceutical Co., Ltd, Shanghai 201203, China
To investigate the efficacy and safety of the novel orally active phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor in relapsed and/or refractory follicular lymphoma (FL) patients who had received at least two prior systemic treatments.Histologically confirmed relapsed and/or refractory FL patients with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg qd, po in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression free survival (PFS), overall survival (OS), disease control rate and drug safety profile. Of 114 screened relapsed and/or refractory FL patients, 84 were enrolled in the full analysis set (FAS).The ORR of 84 FAS patients was 79.8% (95%CI: 69.6-87.8, 67 patients), with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (range: 9.3-15.9). The median PFS was 13.4 months (95%CI: 11.1-16.7). The 12-month OS rate was 91.4% (95%CI: 82.7-95.8. and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%) and interstitial lung disease (3.6%).Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory FL patients who had received at least two prior systemic therapies.
基金：
This trial was funded by Shanghai Yingli Pharmaceutical Co., Ltd. The funding body was
involved in the design of the study, collection, analysis and interpretation of data, writing
the report and the decision to submit the manuscript for publication. This work was
supported by grants from Chinese Academy of Medical Sciences Innovation Fund for
Medical Sciences (2022-I2M-1-022).
第一作者机构：[1]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[2]Tianjin Institutes of Health Science, Tianjin 301600, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[2]Tianjin Institutes of Health Science, Tianjin 301600, China[*1]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China[*2]Tianjin Institutes of Health Science, Tianjin 301600, China
推荐引用方式(GB/T 7714)：
Wang Tingyu,Sun Xiuhua,Qiu Lihua,et al.The oral PI3Kδ inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: A phase 2, single-arm, open-label clinical trial[J].CLINICAL CANCER RESEARCH.2023,29(8):1440-1449.doi:10.1158/1078-0432.CCR-22-2939.
APA：
Wang Tingyu,Sun Xiuhua,Qiu Lihua,Su Hang,Cao Junning...&Qiu Lugui.(2023).The oral PI3Kδ inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: A phase 2, single-arm, open-label clinical trial.CLINICAL CANCER RESEARCH,29,(8)
MLA：
Wang Tingyu,et al."The oral PI3Kδ inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: A phase 2, single-arm, open-label clinical trial".CLINICAL CANCER RESEARCH 29..8(2023):1440-1449
医学