打开APP

NEJM:科学家开发出可安全高效治疗慢性淋巴细胞白血病的新型药物

  1. ACP-196
  2. 依鲁替尼
  3. 慢性淋巴细胞白血病
  4. 药物

来源:生物谷 2015-12-11 14:00

近日,来自俄亥俄州立大学综合性肿瘤中心等机构的癌症研究人员在杂志New England Journal of Medicine刊文表示,一种名为acalabrutinib(ACP-196)的新型药物可以在降低患者最低副作用的同时,帮助促进慢性淋巴细胞

图片来源:medicalxpress.com

2015年12月9日 讯 /生物谷BIOON/ --近日,来自俄亥俄州立大学综合性肿瘤中心等机构的癌症研究人员在杂志New England Journal of Medicine刊文表示,一种名为acalabrutinib(ACP-196)的新型药物可以在降低患者最低副作用的同时,帮助促进慢性淋巴细胞白血病(CLL)患者的应答率。ACP-196是第二代布鲁顿氏酪氨酸激酶(BTK)抑制剂,该药物可以通过永久性结合BTK来发挥作用,BTK是一种特殊蛋白的一部分,而这种特殊蛋白可以从CLL细胞表面将信号传递细胞核中的基因,从而促进癌细胞生存和生长,通过阻断BTK,药物ACP-196就可以抑制CLL细胞的生长信号,直至促进癌细胞死亡。

并不像第一代的BTK抑制剂(比如依鲁替尼),本文研究中研究者发现,新一代的药物acalabrutinib更有选择性地阻断BTK通路,同时还不破坏其它对血小板和免疫功能重要的分子通路,从而就可以避免或者降低和癌症疗法相关副作用的产生。本文研究整合了支持ACP-196选择性的临床前研究和I/II期临床试验,I/II期临床试验中研究者对来自美国和英国6个地方的61名复发的CLL患者进行研究,患者平均年龄为62岁;研究者对人类首次进行临床试验目的在于确定ACP-196对复发CLL患者的药物的推荐剂量、安全性、有效性、药代动力学及药效学。

I期招募的病人接受了增加剂量的药物ACP-196,即每日最大剂量为400mg;而II期临床试验中研究者让患者每天摄入两次100mg剂量的ACP-196,随后通过临床评估、成像测试及血液检测来评估病人的应答率;研究者Bonnie Harrington指出,我们很高兴可以看到如此具有选择性的一种药物可以从临床前的动物模型研究中进入到人体临床试验中,来帮助预测药物对患者的疗效及患者耐受性的改善情况。

早在2013年FDA就加速批准了药物依鲁替尼的使用,依鲁替尼作为首个BTK抑制剂,其可以用于外套细胞淋巴瘤的治疗,而2014年2月份,FDA扩大了对慢性淋巴细胞白血病疗法药物的审批,当然这主要是基于俄亥俄州立大学综合癌症中心的临床前和临床研究数据。BTK抑制剂可以将慢性淋巴细胞白血病从不可治愈转化成为慢性疾病,尤其是CLL的标准疗法可以对患者产生35%至40%的疗法应答率。

最后研究者表示,后期还需要进行大量的临床试验来评估ACP-196对CLL的治疗效应,当然这包括3期的临床试验,将ACP-196同依鲁替尼进行面对面比较来评估ACP-196在治疗CLL中的优势。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。更多资讯请下载生物谷APP.

PMC:

PMID:

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.

Byrd JC1, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR.

Background Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. Methods In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion. Results The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred. Conclusions In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443 .).

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->