Microtubule destabilizer (tubulin polymerization inhibitor) Tumor checkpoint controller Treatment of advanced glioblastoma multiforme

Lisavanbulin (BAL-101553), a prodrug of avanbulin (BAL-27862), is a novel small molecule tubulin-binding agent, promoting tumor cell death through spindle assembly check-point activation, and is currently in phase I/IIa development in advanced glioblastoma multiforme (GBM). Daily contin-uous oral lisavanbulin is well tolerated with an established pharmacokinetic and safety profile. Expression of end-binding protein 1 (EB1), which is involved in microtubule function, has been identified as a potential response-predictive marker for lisavanbulin with profound long-lasting responses seen in EB1+ recurrent GBM. A biomarker-selected phase II study is currently ongoing in patients with recurrent GBM whose archival tumor tissue tests positive for EB1 (NCT02490800); and a combination dose-escalation study with standard of care radiation in patients with newly diagnosed GBM (NCT03250299) is recruiting.