设为首页 |  加入收藏 |  联系我们

如:神经外科 骨科 手外科 眼科 神经内科……

海特生物获准在第62届美国血液学会(ASH)年会上公布原研Ⅰ类新药--沙艾特®(CPT)III期临床试验结果相关数据

 点击次数:165 字体显示:【大】  【中】  【小】

        武汉海特生物制药股份有限公司是一家以打造中国最优的生物创新药企业为目标的高新技术生物制药企业(股票简称:海特生物,股票代码:300683)。公司今日宣布将在第62届美国血液学会(ASH)年会上以口头报告形式公布沙艾特®CPT)联合TD治疗复发或多发性骨髓瘤的期临床试验相关数据。

        本届ASH年会将于20201258日以线上会议的形式举行。

报告标题:

        Circularly Permuted TRAIL (CPT) Combined with Thalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (CPT-MM301)

        沙艾特®CPT)联合沙利度胺和地塞米松治疗复发或难治多发性骨髓瘤:多中心、双盲、随机对照期临床试验(CPT-MM301试验)

报告作者:

        陈文明,主任医师、教授、医学博士,首都医科大学附属北京朝阳医院

报告时间:

        北京时间,127日,星期一,凌晨5

        (美国太平洋时间,126日,星期天,13点)

报告形式:

        Oral

报告编号:

        416

报告频道:

        Channel 10

分会场编号和标题:

        653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Relapsed/Refractory Multiple Myeloma Hematology Disease Topics & Pathways:multiple myeloma, Biological, apoptosis, Adult, Diseases, Therapies, Biological Processes, Plasma Cell Disorders, Lymphoid Malignancies, Study Population, Clinically relevant

        骨髓瘤/淀粉样变性:治疗,不包括移植:复发/难治性多发性骨髓瘤血液学疾病主题和途径:

        多发性骨髓瘤,生物学,凋亡,成人,疾病,治疗,生物学过程,浆细胞疾病,淋巴恶性肿瘤,研究人群,临床相关

Abstract:

        Objective

        CPT, a recombinant permuted human TNF-related apoptosis-inducing ligand (TRAIL), is a first-in-human anti-myeloma drug targeting death receptor 4/5. CPT was found to be a safe and effective anti-myeloma drug as a monotherapy and combined with thalidomide and dexamethasone (TD) in phase 1 and 2 studies for relapsed or refractory multiple myeloma (RRMM) patients. In order to verify the effectiveness and safety of CPT, we have conducted this multi-center, double-blind, placebo-controlled phase 3 study.

        Methods

        In this study, 417 RRMM patients previously treated with two or more lines of therapies were randomly assigned (2:1) to receive CPT+TD (CPT group) vs. placebo+TD (control group) from March 4, 2015 to July 3, 2019 in 36 centers of China.

        CPT or placebo at a dose of 10 mg/kg was intravenously administered on days 1 to 5, both groups receive dexamethasone 40 mg orally on days 1 to 4, and thalidomide 150mg daily, 28 days per cycle until to disease progressions or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR), time to progression (TTP), time to response (TTR), duration of response (DOR), health related quality of life (HRQoL) and safety.

        Results

        Of the 417 patients enrolled, 415 patients received CPT+TD (n=276) or placebo+TD (n=139) treatment. The demographic, baseline disease and clinical characteristic of the two groups were comparable. The median age of the patients was 59 years, and the median time from the initial diagnosis of multiple myeloma (MM) to participating this trial was 2.6 years. The median number of lines of prior therapies was 3. Proteasome inhibitors (PI) and immunomodulators (IMiD) were previously used in 74% and 86.5% of patients, respectively.

        At date cutoff, the primary endpoint of PFS was significantly longer in the CPT group than in the control group (median 5.5 vs. 3.1 months; hazard ratio [HR] 0.619; P<0.0001) (Figure). The key secondary endpoints, including ORR (30.4% vs. 13.7%, P=0.0002) and OS (median 21.8 vs.17.0 months; HR, 0.723; P=0.0166) were also significantly improved in the CPT group than in the control group (Figure). Subgroup analysis of PFS, OS and ORR showed the superiority of CPT+TD over placebo +TD in almost all subgroups (Figure). It is particularly interesting to note that CPT exhibited excellent efficacy consistently with PFS, OS and ORR in the subgroups of patients with a poor prognosis, including those with refractory MM, with previous PI and IMiD therapies, and those received >3 lines of prior therapies. PFS and ORR were also significantly improved in the patients with PI and IMiD double-refractory MM. The other secondary endpoints including TTP, DOR and HRQoL also showed the superiority of the CPT group over the control group. To date of cutoff, the events of disease progressions or death occurred in 203 patients (73.6%) in the CPT group vs.111 patients (79.9%) in the control group.

        The serious adverse events (SAE) rates were similar in the CPT group and the control group (40.6% vs. 37.4%), as were the death rates during the treatments (7.6% vs. 8.6%). Treatment-emergent adverse events (TEAEs) with at least a 10% greater frequency in the CPT group vs. the control group were elevated alanine transaminase (ALT), elevated aspartate transaminase (AST), elevated lactate dehydrogenase (LDH), increased monocyte counts, hypocalcaemia and upper respiratory tract infections. The data suggested that CPT may induce hepatotoxicity in patients, most of which were grade 1 or 2 and reversible. Grade 3 or 4 TEAEs observed in the CPT group and the control group included decreased neutrophil counts (26.8% vs. 26.6%), pneumonia (25% vs. 23.7%) and hyperglycemia (21% vs. 12.2%).

        Conclusions

        This study demonstrated that CPT was an effective drug for the treatment of RRMM patients, even in the multi-line treated MM patients and PI and/or IMIDs refractory MM patients. The combination of CPT with TD significantly prolonged the PFS and OS, increased the ORR. CPT combined with TD was well tolerated, the adverse events were mild, transient and reversible. CPT is expected to be the first available anti-myeloma drug that targets death receptor 4/5.

海特生物简介:

        海特生物立足于神经系统、肿瘤领域用药的研发生产。目前已经上市销售一个国家一类生物新药——注射用鼠神经生长因子(mNGF,金路捷);一个一类基因工程生物新药——重组变构人肿瘤坏死因子相关凋亡诱导配体(Circular Permuted TRAIL简称:CPT)已经完成Ⅲ期临床总结工作,现处于NDA申报准备阶段。

        海特生物秉承“敬畏生命,无畏创新”的企业宗旨,践行“正直、感恩、专业、进取”的企业价值观,力争成为中国最优的创新药企业。公司将在大分子药物、小分子药物、体外诊断等领域进行拓展,以服务患者为己任,以持续创新为先导,将海特生物打造成一流的医药企业集团!