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

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 wer...

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Vydané v:Cell reports. Medicine Ročník 6; číslo 6; s. 102165
Hlavní autori: 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
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Elsevier Inc 17.06.2025
Elsevier
Predmet:
Administration, Oral
Adult
Advanced Basic Science
Aged
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
astrocytoma
Biomarkers, Tumor - metabolism
Brain Neoplasms - drug therapy
Brain Neoplasms - pathology
Dose-Response Relationship, Drug
Female
glioblastoma
Glioblastoma - drug therapy
Glioblastoma - metabolism
Glioblastoma - pathology
glioma
Glioma - drug therapy
Glioma - metabolism
Glioma - pathology
Humans
lisavanbulin
Male
Middle Aged
Neoplasm Grading
glioma
glioblastoma
lisavanbulin
astrocytoma
ISSN:2666-3791, 2666-3791
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Shrnutí: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). [Display omitted] •Lisavanbulin is an orally dosed brain-penetrant mitotic spindle checkpoint inhibitor•Our study assesses lisavanbulin in refractory astrocytoma or glioblastoma•Lisavanbulin is tolerable in patients with these tumors•A subset of patients have durable efficacy responses to lisavanbulin Lopez et al. report a phase 1/2a study evaluating once-daily oral lisavanbulin, a brain-penetrant microtubule-targeting agent in patients with solid tumors or recurrent high-grade glioma. Lisavanbulin is tolerable in these patients and is associated with profound, durable responses in a subset of patients with grade 4 astrocytoma or glioblastoma.
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ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2025.102165