机构：[1]Peking University Cancer Hospital & Institute, Beijing, China[2]Fudan University Shanghai Cancer Center, Shanghai, China[3]The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China[4]The First Affiliated Hospital of Soochow University, Suzhou, China[5]Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China[6]Tianjin Medical University Cancer Institute & Hospital, Tianjin, China[7]Guangdong Provincial Peoples Hospital, Guangzhou, China广东省人民医院[8]The Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院[9]Peking University Third Hospital, Beijing, China[10]Henan Cancer Hospital, Zhengzhou, China河南省肿瘤医院[11]Beijing Shijitan Hospital Affiliated of Capital Medical University, Beijing, China[12]Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China华中科技大学同济医学院附属协和医院[13]Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China[14]West China Hospital of Sichuan University, Chengdu, China四川大学华西医院[15]Zhejiang Cancer Hospital, Hangzhou, China浙江省肿瘤医院[16]The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China浙江大学医学院附属第一医院[17]Hunan Cancer Hospital, Changsha, China[18]Fujian Medical University Union Hospital, Fuzhou, China[19]HUTCHMED Limited, Shanghai, China
Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with antitumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/refractory mature Bcell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase 2 dose (RP2D). Overall, 134 Chinese patients were enrolled (dose escalation, n=27; dose expansion, n=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% CI, 37.5-64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the doseexpansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased doseproportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed antitumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.
第一作者机构：[1]Peking University Cancer Hospital & Institute, Beijing, China
通讯作者：
推荐引用方式(GB/T 7714)：
Song Yuqin,Cao Junning,Zhang Qingyuan,et al.Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors[J].REVISTA CHILENA DE LITERATURA.2024,(109):2165-2176.doi:10.3324/haematol.2022.282401.
APA：
Song Yuqin,Cao Junning,Zhang Qingyuan,Li Caixia,Qiu Lugui...&Zhu Jun.(2024).Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.REVISTA CHILENA DE LITERATURA,,(109)
MLA：
Song Yuqin,et al."Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors".REVISTA CHILENA DE LITERATURA ..109(2024):2165-2176
