Phase 1/2 Trial Of Bevacizumab Plus Tpi 287, A Brain Penetrable Anti-Microtubule Agent, In Patients With Recurrent Glioblastoma.

2055Background: Microtubule inhibitors have demonstrated efficacy in preclinical models of glioblastoma (GBM), however, clinical benefit is hampered by subtherapeutic dose delivery. Designed to overcome this limitation, TPI 287 is a third-generation taxane that readily penetrates the blood brain barrier and evades mechanisms of P-glycoprotein mediated efflux. CB-017 is a multi-center phase 1/2 trial designed to determine the maximum tolerated dose and potential efficacy in patients treated with TPI 287 plus bevacizumab (BEV) for treatment of recurrent GBM. Results of the recently completed dose escalation stage of the trial are reported. Methods: GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. BEV was administered at 10 mg/kg every 2 weeks and TPI 287 every 3 weeks via IV infusion. MRIs were obtained every six weeks with response assessed via RANO. TPI-287 dose escalation was based upon a standard 3+3 design....