小柯机器人

切换到桌面版
阿瓦普替尼治疗晚期系统性肥大症的安全性和疗效的1期临床试验
2021-12-11 11:00
来源：小柯机器人

美国丹娜·法伯癌症研究所Daniel J. DeAngelo等研究人员完成阿瓦普替尼治疗晚期系统性肥大症的安全性和疗效的1期临床试验。2021年12月6日，国际知名学术期刊《自然—医学》在线发表了这一成果。

研究人员通过一项1期研究（NCT02561988）评估了阿瓦普替尼（BLU-285），一种选择性的KIT D816V抑制剂，用于晚期系统性肥大细胞增多症（AdvSM）患者。主要终点是阿瓦普利尼的最大耐受剂量、推荐的2期剂量和安全性。次要终点包括总反应率和肥大细胞负担评估的变化。在86名患者中评估了阿瓦普替尼的剂量，每天一次，每次30-400毫克，其中69名患者为中心确认的AdvSM。没有达到最大耐受剂量，在剂量扩大的队列中研究了每天200毫克和300毫克。观察到的最常见的不良事件是眼眶周围水肿（69%）、贫血（55%）、腹泻（45%）、血小板减少（44%）和恶心（44%）。
总的来说，13%的患者发生了颅内出血，但在没有严重血小板减少（血小板<50×109/l）的患者中，只有1%发生了颅内出血。在53名有反应价值的患者中，总反应率为75%。完全缓解率为36%。在92%和99%的患者中，阿瓦普替尼分别使骨髓肥大细胞和血清胰蛋白酶减少了≥50%。阿瓦普替尼诱导了深度和持久的反应，包括AdvSM患者的KIT D816V的分子缓解，并且在推荐的2期剂量每天200毫克时耐受性良好。
 
据介绍，AdvSM是一种由KIT D816V突变驱动的罕见血液肿瘤，与生存率低有关。
 
附：英文原文
 
Title: Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial

Author: DeAngelo, Daniel J., Radia, Deepti H., George, Tracy I., Robinson, William A., Quiery, Albert T., Drummond, Mark W., Bose, Prithviraj, Hexner, Elizabeth O., Winton, Elliott F., Horny, Hans-Peter, Tugnait, Meera, Schmidt-Kittler, Oleg, Evans, Erica K., Lin, Hui-Min, Mar, Brenton G., Verstovsek, Srdan, Deininger, Michael W., Gotlib, Jason

Issue&Volume: 2021-12-06

Abstract: Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (NCT02561988) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30–400mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200mg and 300mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50×109/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200mg daily.

DOI: 10.1038/s41591-021-01538-9

Source: https://www.nature.com/articles/s41591-021-01538-9

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

分享到:

0