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阿瓦普替尼对晚期系统性肥大细胞增多症的疗效和安全性的2期临床试验
2021-12-11 11:01
来源：小柯机器人

美国斯坦福大学Jason Gotlib等研究人员完成阿瓦普替尼对晚期系统性肥大细胞增多症（AdvSM）的疗效和安全性的2期临床试验。这一研究成果于2021年12月6日在线发表在国际学术期刊《自然—医学》上。

研究人员报告了一项正在进行的阿瓦普替尼的关键性单臂2期试验（编号：NCT03580655）的预设中期分析结果，阿瓦普替尼是一种强效、选择性的KIT D816V抑制剂，主要以每天一次的起始剂量200毫克给药于AdvSM患者（n=62）。主要终点是总反应率（ORR）。次要终点包括AdvSM-症状评估表总症状评分和生活质量的平均基线变化、反应时间、反应持续时间、无进展生存期、总生存期、疾病负担措施的变化和安全性。
 
主要终点成功达到（P=1.6×10-9），在32名有反应价值的AdvSM患者中，ORR为75%（95%置信区间为57-89），这些患者有足够的随访以评估反应，包括19%的完全缓解和全部或部分血液学恢复。观察到血清胰蛋白酶（93%）、骨髓肥大细胞（88%）和KIT D816V变异等位基因部分（60%）比基线减少了≥50%。最常见的≥3级不良事件是中性粒细胞减少症（24%）、血小板减少症（16%）和贫血（16%）。阿瓦普替尼显示出较高的临床、形态和分子反应率，并且在AdvSM患者中普遍具有良好的耐受性。
 
据悉，AdvSM是一种罕见的、由KIT D816V驱动的血液肿瘤，其特点是肥大细胞浸润和生存期缩短。
 
附：英文原文

Title: Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial

Author: Gotlib, Jason, Reiter, Andreas, Radia, Deepti H., Deininger, Michael W., George, Tracy I., Panse, Jens, Vannucchi, Alessandro M., Platzbecker, Uwe, Alvarez-Twose, Ivn, Mital, Andrzej, Hermine, Olivier, Dybedal, Ingunn, Hexner, Elizabeth O., Hicks, Lisa K., Span, Lambert, Mesa, Ruben, Bose, Prithviraj, Pettit, Kristen M., Heaney, Mark L., Oh, Stephen T., Sen, Jayita, Lin, Hui-Min, Mar, Brenton G., DeAngelo, Daniel J.

Issue&Volume: 2021-12-06

Abstract: Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200mg in patients with AdvSM (n=62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM–Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (P=1.6×10-9), with an ORR of 75% (95% confidence interval 57–89) in 32response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of ≥50% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and KIT D816V variant allele fraction (60%) were observed. The most frequent grade≥3 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM.

DOI: 10.1038/s41591-021-01539-8

Source: https://www.nature.com/articles/s41591-021-01539-8

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章：《自然—医学》：Online/在线发表

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