抗体-药物偶联物
耐火材料(行星科学)
CD19
结合
抗体
医学
药品
淋巴细胞白血病
急性淋巴细胞白血病
白血病
癌症研究
肿瘤科
免疫学
内科学
药理学
单克隆抗体
生物
数学分析
天体生物学
数学
作者
Nitin Jain,Wendy Stock,Amer M. Zeidan,Ehab Atallah,James McCloskey,Leonard T. Heffner,Benjamin Tomlinson,Bhavana Bhatnagar,Jay Feingold,David Ungar,Grace Chao,Xiaoyan Zhang,Yajuan Qin,Karin Havenith,Hagop M. Kantarjian,Matthew J. Wieduwilt
出处
期刊:Blood Advances
[Elsevier BV]
日期:2020-02-03
卷期号:4 (3): 449-457
被引量:53
标识
DOI:10.1182/bloodadvances.2019000767
摘要
Abstract Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge. Loncastuximab tesirine is an antibody-drug conjugate against CD19, an antigen expressed in many B-cell malignancies. This open-label, single-arm, dose-escalation, dose-expansion study assessed the safety, tolerability, pharmacokinetics (PKs), immunogenicity, and preliminary clinical activity of loncastuximab tesirine in adults with R/R B-ALL. A total of 35 patients were enrolled, with a median age of 55 years (range, 20-80) and a median of 3 prior therapies (range, 1-15). All patients received at least 1 IV infusion of loncastuximab tesirine at 15 to 150 μg/kg once every 3 weeks (Q3W; n = 30) or 50 μg/kg IV weekly (n = 5). Common treatment-emergent adverse events (TEAEs) were nausea (42.9%), febrile neutropenia (37.1%), and reversible liver test abnormalities. Grade ≥3 TEAEs were reported in 85.7% patients, most commonly febrile neutropenia and other hematologic abnormalities and reversible liver test abnormalities. There were no treatment-related deaths. Four patients (11.4%) had grade 2 infusion-related reactions, and 1 patient (150 μg/kg Q3W) had a dose-limiting toxicity of hyperbilirubinemia that resolved within 6 days without further action. The maximum tolerated dose was not reached. Three patients achieved complete responses, 1 each at 30, 120, and 150 μg/kg Q3W. PK studies showed marked interpatient variability, with target-mediated drug disposition seeming to contribute to time- and dose-dependent disposition. No clinically relevant anti–drug-antibody formation occurred. The trial was terminated in the dose-escalation phase because of slow accrual. This trial was registered at www.clinicaltrials.gov as NCT02669264.
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