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Clinical Trial
. 2025 Jun 17;6(6):102165.
doi: 10.1016/j.xcrm.2025.102165.

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

Juanita Suzanne Lopez  1 , Simon Haefliger  2 , Ruth Plummer  3 , Paul M Clement  4 , Thomas R Jeffry Evans  5 , Heinz Läubli  6 , Patrick Roth  7 , Rebecca Kristeleit  8 , Lucy Brazil  9 , Ghazaleh Tabatabai  10 , Antje Wick  11 , Benjamin Wunderlich  12 , Kirk Beebe  13 , Joel Robert Eisner  13 , Heidi Lane  14 , Marc Engelhardt  14 , Thomas Kaindl  15 , Peter Hau  16 , Thomas Hundsberger  17 , Joachim Steinbach  18
Affiliations
Clinical Trial

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

Juanita Suzanne Lopez et al. Cell Rep Med. .

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).

Keywords: astrocytoma; glioblastoma; glioma; lisavanbulin.

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Conflict of interest statement

Declaration of interests T.K., M.E., and H. Lane are employees of Basilea Pharmaceutica International Ltd.

Figures

None
Graphical abstract
Figure 1
Figure 1
Patient flow and determination of MTD in patients with advanced or recurrent solid tumors and in patients with GBM or high-grade glioma in phase 1 (MTD-determining population) See also Tables S1–S7.
Figure 2
Figure 2
Pharmacokinetic profile of patients with GBM or high-grade glioma (N = 46) on cycle 1 day 1 Circles represent values for each patient. Boxes represent quartiles (25%, 50%, 75%) and whiskers the outliers. See also Figures S1 and S2; Table S8.
Figure 3
Figure 3
Treatment duration, best objective response, IDH status (wt, wild type; mt, mutation; ○, unknown), and EB1 status (+, positive; −, negative; ○, unknown) of patients with GBM or high-grade glioma in study CDI-CS-002 and study CDI-CS-003 For patients with objective response (P1, P2, P4, and P5) and near objective response (P3), see also Figures 4 and S3. Note: the study design uses the 2016 WHO classification, and therefore, based on the 2021 classification, some patients would not be considered to have GBM.
Figure 4
Figure 4
Five-gene response classifier based on GBM samples from study CDI-CS-002 (n = 15) and study CDI-CS-003 (n = 1) RNA sequencing was performed for patients where adequate tissue samples were available for analysis, who had GBM according to WHO 2016 criteria, had received doses where responses had been observed (i.e., 20–30 mg/day), and had not been discontinued for reasons other than radiologically confirmed disease progression.
Figure 5
Figure 5
Prevalence of the five-gene response classifier in TCGA GBM database
See this image and copyright information in PMC

References

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