Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study

Abstract

Purpose. Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m2. Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study. Methods. This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle. Results. Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360.

Interaction of norsecurinine-type monomeric and dimeric alkaloids with α-tubulin: a molecular docking study

“…New MTAs are regularly proposed, including synthetic molecules such as stilbene and quinolinamine derivatives [53,54], synthetic products derived from a marine source, such as plinabulin and zampanolide derivatives [55,56], and many others. Among the newest MTAs, a promising drug candidate is lisavanbulin as the prodrug of avanbulin, currently evaluated in patients with advanced cancers, notably those with ovarian tumour or glioblastoma [57]. In experimental models, this compound (also known as BAL101553) has shown good brain penetration and robust antitumor activity alone or in combination with radiotherapy or temozolomide-based chemotherapy [58,59].…”