A phase 1/2a dose-finding study and biomarker assessment of oral lisavanbulin in patients with high-grade glioma or glioblastoma.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-06-17 DOI:10.1016/j.xcrm.2025.102165

Juanita Suzanne Lopez, Simon Haefliger, Ruth Plummer, Paul M Clement, Thomas R Jeffry Evans, Heinz Läubli, Patrick Roth, Rebecca Kristeleit, Lucy Brazil, Ghazaleh Tabatabai, Antje Wick, Benjamin Wunderlich, Kirk Beebe, Joel Robert Eisner, Heidi Lane, Marc Engelhardt, Thomas Kaindl, Peter Hau, Thomas Hundsberger, Joachim Steinbach

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引用次数: 0

Abstract

Lisavanbulin is a prodrug of the microtubule-targeting agent avanbulin. Both avanbulin and lisavanbulin have demonstrated significant antitumor activity in several preclinical tumor models including glioblastoma. Previous human studies demonstrated that 48-h infusions of intravenous lisavanbulin were well tolerated with preliminary activity in recurrent glioblastoma. The current phase 1/2a study evaluates the safety and tolerability of once-daily oral lisavanbulin in patients with solid tumors or recurrent glioblastoma or high-grade glioma. Lisavanbulin is associated with profound, durable responses in a subset of patients with recurrent refractory grade 4 astrocytoma or glioblastoma. We present here the clinical and translational results from this trial, including a description of a response-predictive molecular signature that warrants further exploration in these tumor types of significant unmet need. The study is registered at ClinicalTrials.gov (NCT02490800).

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高级别胶质瘤或胶质母细胞瘤患者口服lisavanbulin的1/2a期剂量研究和生物标志物评估

Lisavanbulin是微管靶向药物avanbulin的前药。在包括胶质母细胞瘤在内的几种临床前肿瘤模型中，avanbulin和lisavanbulin都显示出显著的抗肿瘤活性。先前的人体研究表明，静脉滴注lisavanbulin 48小时耐受性良好，对复发性胶质母细胞瘤具有初步活性。目前的1/2a期研究评估了每日一次口服lisavanbulin对实体瘤或复发性胶质母细胞瘤或高级别胶质瘤患者的安全性和耐受性。Lisavanbulin在复发的难治性4级星形细胞瘤或胶质母细胞瘤患者中具有深远、持久的疗效。我们在此介绍该试验的临床和转化结果，包括对反应预测分子特征的描述，该特征值得在这些未满足需求的肿瘤类型中进一步探索。该研究已在ClinicalTrials.gov注册（NCT02490800）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.