复发或难治性 B 细胞非霍奇金淋巴瘤患者使用 CD20 单克隆抗体与 SIRPα 的 CD47 结合域的融合蛋白 amulirafusp alfa (IMM0306) 的安全性和疗效:1/2 期研究

IF 29.5 1区 医学 Q1 HEMATOLOGY
Jianliang Yang, Yongping Song, Keshu Zhou, Zhiming Li, Mingzhi Zhang, Hongmei Jing, Zhen Wang, Li Yu, Wei Meng, Qiying Lu, Wenzhi Tian, Yuankai Shi
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引用次数: 0

摘要

amulrafusp alfa (IMM0306)是信号调节蛋白α (SIRPα) CD47结合域与CD20单克隆抗体在两条重链上的融合蛋白。本研究旨在评估阿穆利拉法治疗复发或难治性(r/r) b细胞非霍奇金淋巴瘤(B-NHL)的安全性和初步疗效。我们招募了CD20 + r/r B-NHL患者,这些患者之前接受过至少两条线的治疗,在前2周接受单剂量阿穆利拉法,随后是多剂量期,患者在4周的周期中每周接受相同的静脉注射剂量。主要终点是评估安全性,确定amulrafusp α的最大耐受剂量(MTD)和推荐的2期剂量(RP2D)。在2020年5月22日至2022年2月10日期间,入选48例r/r B-NHL患者,接受40 ~ 2000 μg/kg剂量的阿穆利拉法素治疗。截至2024年4月18日数据截止日期,未观察到剂量限制性毒性,未达到MTD。鉴定剂量为2000 μg/kg为RP2D。所有级别和≥3级治疗相关不良事件(TRAEs)分别发生在48例(100%)和33例(68.8%)患者中。最常见的≥3级TRAEs为淋巴细胞计数减少(28/48,58.3%)、白细胞计数减少(10/48,20.8%)、绝对中性粒细胞计数减少(9/48,18.8%)和贫血(5/48,10.4%)。在800 ~ 2000 μg/kg剂量下,滤泡性淋巴瘤和边缘带淋巴瘤的客观有效率分别为41.2%(7/17,95%可信区间[CI] 18.4 ~ 67.1)和33.3% (2/6,95% CI 3.7 ~ 71.0)。amulrafusp在r/r B-NHL患者中显示出良好的安全性和初步疗效,值得进一步研究。试验注册NCT05805943。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and efficacy of amulirafusp alfa (IMM0306), a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a phase 1/2 study
Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles. The primary endpoints were to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of amulirafusp alfa. Between May 22, 2020 and February 10, 2022, 48 patients with r/r B-NHL were enrolled and received amulirafusp alfa at the doses of 40–2000 μg/kg. As of the data cut-off date of April 18, 2024, no dose-limiting toxicity was observed, and the MTD was not reached. The dose of 2000 μg/kg was identified as the RP2D. All grades and ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 48 (100%) and 33 (68.8%) patients, respectively. The most common ≥ grade 3 TRAEs were lymphocyte count decreased (28/48, 58.3%), white blood cell count decreased (10/48, 20.8%), absolute neutrophil count decreased (9/48, 18.8%) and anemia (5/48, 10.4%). At the doses of 800–2000 μg/kg, objective response rate in follicular lymphoma and marginal zone lymphoma was 41.2% (7/17, 95% confidence interval [CI] 18.4–67.1) and 33.3% (2/6, 95% CI 3.7–71.0), respectively. Amulirafusp alfa showed favorable safety profile and preliminary efficacy in patients with r/r B-NHL, meriting further investigation. Trial registration NCT05805943.
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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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