ATNT-08CB-017: A PHASE 1/2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, IN PATIENTS WITH RECURRENT GLIOBLASTOMA NAÏVE TO ANTI-ANGIOGENIC THERAPY

BACKGROUND: TPI 287, a third-generation taxane that readily penetrates the blood brain barrier, is under investigation for the treatment of recurrent glioblastoma (GBM). CB-017 is a dose-escalation phase 1/2 multi-center trial designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with bevacizumab (BEV) in patients without prior exposure to angiogenesis inhibitors. Interim 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. BEV 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. 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. RESULTS: As of June 2015, 21 patients have been enrolled in 6 dose-escalation cohorts (140-200 mg/sq m). No DLTs have been observed to date, with myelosuppression (n = 2) as the only drug-related grade 3/4 adverse event reported. Among the 17 patients evaluable for response, 9 (53%) achieved objective response (2 CR, 7 PR) and 7 had stable disease. Median and 6-month PFS are 5.5 months [95% C.I. 4.1-10.7] and 38%, respectively. Median overall survival is 12.9 months [95% C.I. 12.2-NR] and 1-year survival is 73% after a median follow-up of 12.4 mo. CONCLUSION: TPI 287 is safe and potentially efficacious in combination with bevacizumab for the treatment of recurrent GBM. Updated safety and efficacy results will be presented.