Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study

作者全名：Xu, Min; Shu, Jinhui; Qian, Shenxian; Guo, Jingming; Gong, Yuping; Huang, Ruibin; Wang, Shuye; Zhou, Zeping; Yuan, Guolin; Huang, Meijuan; Lin, Li -E; Lou, Shifeng; Song, Yanping; Liu, Qingchi; Zhou, Hu; Mei, Heng; Hu, Yu

作者地址：[Xu, Min; Shu, Jinhui; Mei, Heng; Hu, Yu] Huazhong Univ Sci & Technol, Union Hosp, Inst Hematol, Tongji Med Coll, Wuhan, Peoples R China; [Qian, Shenxian] Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Dept Hematol, Sch Med, Hangzhou, Peoples R China; [Guo, Jingming] China Three Gorges Univ, Yichang Cent Peoples Hosp, Coll Clin Med Sci 1, Dept Hematol, Yichang, Peoples R China; [Gong, Yuping] Sichuan Univ, Dept Hematol, West China Hosp, Chengdu, Peoples R China; [Huang, Ruibin] Nanchang Univ, Affiliated Hosp 1, Dept Hematol, Nanchang, Peoples R China; [Wang, Shuye] Harbin Med Univ, Affiliated Hosp 1, Dept Hematol, Harbin, Peoples R China; [Zhou, Zeping] Kunming Med Univ, Affiliated Hosp 1, Dept Hematol, Kunming, Peoples R China; [Yuan, Guolin] Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Dept Hematol, Affiliated Hosp, Xiangyang, Peoples R China; [Huang, Meijuan] Fujian Med Univ, Dept Hematol, Union Hosp, Fuzhou, Peoples R China; [Lin, Li -E] Hainan Prov Peoples Hosp, Dept Hematol, Haikou, Peoples R China; [Lou, Shifeng] Chongqing Med Univ, Affiliated Hosp 2, Dept Hematol, Chongqing, Peoples R China; [Song, Yanping] Xian Cent Hosp, Dept Hematol, Xian, Peoples R China; [Liu, Qingchi] Hebei Med Univ, Hosp 1, Dept Hematol, Shijiazhuang, Peoples R China; [Zhou, Hu] Zhengzhou Univ, Affiliated Canc Hosp, Henan Canc Hosp, Dept Hematol, Zhengzhou, Peoples R China; [Mei, Heng] Huazhong Univ Sci & Technol, Union Hosp, Inst Hematol, Tongji Med Coll,Hubei Clin Med Ctr Cell Therapy Ne, 1277 Jiefang Ave, Wuhan 430022, Peoples R China

通信作者：Mei, H (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Inst Hematol, Tongji Med Coll,Hubei Clin Med Ctr Cell Therapy Ne, 1277 Jiefang Ave, Wuhan 430022, Peoples R China.

来源：LANCET REGIONAL HEALTH-WESTERN PACIFIC

ESI学科分类：　

WOS号：WOS:001245163000001

JCR分区：Q1

影响因子：7.6

年份：2024

卷号：47

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Immune thrombocytopenia; Zuberitamab; Rituximab; Safety and efficacy

摘要：Background Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces longterm effect as second -line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods This randomised, double-blind, placebo -controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 x 10(9)/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once -weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count >= 50 x 10(9)/L at week 8. Secondary endpoints include the proportion of patients with platelet counts >= 50 x 10(9)/L or >= 100 x 10(9)/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as >= 30 x 10(9)/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT >= 50 x 10(9)/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count >= 50 x 10(9)/L or >= 100 x 10(9)/L or an increase twice more than baseline as well as >= 30 x 10(9)/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates.

基金机构：National Natural Science Foundation of China [82330005, 82070124]; National Key R&D Program of China [2022YFC2502704]; Technology innovation plan key research and development projects of Hubei Prov-ince [2023BCB019]

基金资助正文：<B>Acknowledgements</B> This work was supported by Grants from the National Natural Science Foundation of China (No. 82330005, No. 82070124) , the National Key R&D Program of China (No. 2022YFC2502704) and the Technology innovation plan key research and development projects of Hubei Prov-ince (No. 2023BCB019) . The authors would like to thank all the study investigators and coordinators.