Lopez Juanita Suzanne, Haefliger Simon, Plummer Ruth, Clement Paul M, Jeffry Evans Thomas R, Läubli Heinz, Roth Patrick, Kristeleit Rebecca, Brazil Lucy, Tabatabai Ghazaleh, Wick Antje, Wunderlich Benjamin, Beebe Kirk, Eisner Joel Robert, Lane Heidi, Engelhardt Marc, Kaindl Thomas, Hau Peter, Hundsberger Thomas, Steinbach Joachim
Drug Development Unit at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, Sutton, UK.
Inselspital, Bern University Hospital, University of Bern, Department of Medical Oncology, Bern, Switzerland.
Cell Rep Med. 2025 Jun 17;6(6):102165. doi: 10.1016/j.xcrm.2025.102165.
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).
利沙万布林是一种靶向微管药物阿万布林的前体药物。阿万布林和利沙万布林在包括胶质母细胞瘤在内的多种临床前肿瘤模型中均显示出显著的抗肿瘤活性。先前的人体研究表明，静脉注射利沙万布林48小时的给药方式耐受性良好，对复发性胶质母细胞瘤有初步活性。当前的1/2a期研究评估了每日一次口服利沙万布林在实体瘤、复发性胶质母细胞瘤或高级别胶质瘤患者中的安全性和耐受性。利沙万布林在一部分复发性难治性4级星形细胞瘤或胶质母细胞瘤患者中可产生深刻、持久的反应。我们在此展示该试验的临床和转化结果，包括一种反应预测分子特征的描述，该特征值得在这些有重大未满足需求的肿瘤类型中进一步探索。该研究已在ClinicalTrials.gov（NCT02490800）注册。
