Introduction
advanced/recurrent solid, glioblastoma, tumors, vascular toxicity
GLIOBLASTOMA
Microtubule-targeting agents (MTAs) are among the most effective cytotoxic chemotherapy agents, and affect microtubule dynamics either as microtubule-destabilizers (such as the vinca-alkaloids) or microtubule stabilizers (such as the taxanes and azaepothilone B) [Lisavanbulin (BAL101553; PubChem CID: 45,259,014) is the water-soluble lysine pro-drug of avanbulin (BAL27862; PubChem CID: 11,176,685) [Avanbulin showed activity in a number of Study CDI-CS-003, a single-agent, open-label, Phase 1/2a study performed in two parts, aimed to reconcile these aspects of lisavanbulin’s pharmacokinetics through the use of an extended 48-hour IV infusion to maximize exposure while minimizing vascular toxicity. Part 1 of the study (previously reported) was a Phase 1 dose-escalation portion to determine the maximum tolerated dose (MTD) in patients with advanced/recurrent solid tumors [The work reported here is from Part 2 of study CDI-CS-003, a Phase 2a expansion portion to further characterize the safety and tolerability of lisavanbulin at the MTD of 70 mg/mPatients with glioblastoma were not included in Phase 1, but daily oral administration of lisavanbulin was already under investigation as a monotherapy in patients with recurrent glioblastoma in study CDI-CS-002 (NCT02490800 [