AT-24 * PHASE 1/2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: TPI 287, a novel anti-microtubule agent of the taxoid class that readily penetrates the blood-brain barrier, is under investigation for the treatment of recurrent glioblastoma (GBM). A dose-escalation Phase 1/2 trial was designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with bevacizumab. Initial results from the dose escalation stage of the trial are reported here. METHODS: Patients with GBM at first relapse after standard therapy without prior exposure to anti-angiogenic agents are eligible for enrollment. Bevacizumab is administered at 10 mg/kg as an IV infusion once every 2 weeks. TPI 287 is administered as a 1-hour IV infusion every 3 weeks. Employing a standard 3 + 3 design, dose escalation of TPI 287 is planned until a dose-limiting toxicity (DLT) is observed in order to select the recommended Phase 2 dose. MRIs are obtained at the end of every six-week cycle with response assessment via RANO criteria. RESULTS: As of June 2014, a total of 9 subjects have been enrolled in the first 3 dose-escalation cohorts (140, 150, and 160 mg/m2). No DLTs have been observed to date, and no drug-related grade 3/4 adverse events have been reported. Among the 7 patients evaluable for response, 3 achieved a partial response, and 2 had stable disease (1 confirmed, 1 unconfirmed). Four of these first 9 patients remain on study 39 weeks after start of the trial. TPI 287 dose escalation continues. CONCLUSIONS: Preliminary data to date indicate that TPI 287 is safe in combination with bevacizumab for the treatment of recurrent GBM. Evolving safety and efficacy results will be presented.