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umbralisib

肿瘤

关键词肿瘤 药物 PI3Kδ抑制剂

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解析

Umbralisib 

释    义   n. 新型的、第二代PI3Kδ抑制剂

例    句   The combination of ublituximab, umbralisib, and ibrutinib seems to be tolerable and is associated with encouraging activity in advanced chronic lymphocytic leukaemia and B-cell non-Hodgkin lymphoma. 联合ublituximab、umbralisib和依鲁替尼似乎是可以耐受的,并且与在晚期慢性淋巴细胞白血病和B细胞非霍奇金淋巴瘤的潜在活性密切相关。

概述

Umbralisib (TGR-1202)是第二代PI3Kδ抑制剂,是由TG Therapeutics研发生产。Umbralisib在选择性抑制PI3Kδ的同时也能特异性抑制Casein激酶-1ε(CK1ε),其耐受性有别于早期的PI3Kδ抑制剂。I类PI3Ks是一类膜为基础的酶家族,包含一个由α、β、γ和δ四种同种型组成的p110级联亚单位,能够级联激活信号调节细胞增殖、分化和生存。PI3Kα和PI3Kβ同种型广泛表达,而PI3Kγ和PI3Kδ主要限制性的表达于造血干细胞。在B细胞发育过程

Tolerability and activity of ublituximab, umbralisib, and ibrutinib in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: a phase 1 dose escalation and expansion trial复制标题

Ublituximab,umbralisib和ibrutinib在慢性淋巴细胞白血病和非霍奇金淋巴瘤患者中的耐受性和活性: 1期剂量递增和扩展试验

发表时间:2019-02-05

影响因子:12.0

作者: Loretta J Nastoupil

期刊:Lancet Haematol

We enrolled 46 patients: 24 in the dose-escalation cohort and 22 in the dose-expansion cohort. 46 patients received at least one dose of study drug. The maximum tolerated dose of umbralisib was not reached. The recommended dose for the dose-expansion phase was umbralisib 800 mg orally once daily plus ibrutinib orally once daily and intravenous ublituximab 900 mg administered on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, and on day 1 of cycles 9 and 12. 37 (84%) of 44 patients achieved an overall response (complete or partial response). The most common any-grade adverse events were diarrhoea (n=27 [59%]), fatigue (n=23 [50%]), infusion-related reaction (n=20 [43%]), dizziness (n=17 [37%]), nausea (n=17 [37%]), and cough (n=16 [35%]). Grade 3-4 adverse events were manageable with the most common being   (n=10 [22%]) and cellulitis (n=6 [13%]). Serious adverse events occurred in 11 (24%) of 46 patients and included rash (n=2 [4%]), pneumonia (n=2 [4%]), atrial fibrillation (n=2 [4%]), sepsis (n=2 [4%]), abdominal pain (n=1 [2%]), syncope (n=1 [2%]), cellulitis (n=1 [2%]), pneumonitis (n=1 [2%]), headache (n=1 [2%]), lung infection (n=1 [2%]), skin infection (n=1 [2%]), pleural effusion (n=1 [2%]), pericardial infusion (n=1 [2%]), upper gastrointestinal bleeding (n=1 [2%]), diarrhoea (n=1 [2%]), and weakness (n=1 [2%]).

译文

我们招募了46名患者:剂量增加队列中的24名患者和剂量增加队列中的22名患者。 46名患者接受了至少一剂研究药物。未达到umbralisib的最大耐受剂量。剂量扩展阶段的推荐剂量为:每天一次口服umbralisib 800 mg,口服ibrutinib每天一次,在第1周期的第1、8、15天,第2-6周期的第1天以及第2天,静脉给予ublituximab 900 mg 9和12期中的1例达到44例,其中37例(84%)达到总体缓解(完全或部分缓解)。最常见的任何等级的不良事件为腹泻(n = 27 [59%]),疲劳(n = 23 [50%]),输液相关反应(n = 20 [43%]),头晕(n = 17) [37%]),恶心(n = 17 [37%])和咳嗽(n = 16 [35%])。 3-4级不良事件是可以控制的,最常见的是n = 10 [22%]和蜂窝织炎(n = 6 [13%])。 46名患者中有11名(24%)发生了严重的不良事件,包括皮疹(n = 2 [4%]),肺炎(n = 2 [4%]),房颤(n = 2 [4%]),败血症(n = 2 [4%]),腹痛(n = 1 [2%]),晕厥(n = 1 [2%]),蜂窝织炎(n = 1 [2%]),肺炎(n = 1 [2] 2%]),头痛(n = 1 [2%]),肺部感染(n = 1 [2%]),皮肤感染(n = 1 [2%]),胸腔积液(n = 1 [2%] ),心包输液(n = 1 [2%]),上消化道出血(n = 1 [2%]),腹泻(n = 1 [2%])和无力(n = 1 [2%])。