ET-12 * PHASE II STUDY OF ONARTUZUMAB PLUS BEVACIZUMAB VERSUS PLACEBO PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: Glioblastomas are highly vascularized with elevated VEGF expression and have been shown to respond to the anti-VEGF antibody bevacizumab. High MET expression has been associated with shorter progression-free survival (PFS) in glioblastomas (Pierscianek, et al. Brain Pathol 2013). This phase II study investigated the monovalent MET inhibitor, onartuzumab, plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pl + Bev) in recurrent glioblastoma. METHODS: Bevacizumab-naive patients with glioblastoma at first recurrence following chemoradiation were randomized 1:1 to receive Ona (15mg/kg, q3w) + Bev (15mg/kg, q3w) or Pl + Bev until disease progression. Enrollment onto a third arm, Ona + Pl, was put on hold during assessment of safety data and was subsequently closed due to study conduct concerns (data not presented). Primary endpoint: PFS by RANO criteria (ITT and MET biomarker-positive subpopulations). Secondary endpoints: overall survival, objective response rate, duration of response, and safety. RESULTS: In the 129 patients enrolled (Ona + Bev n = 64, Pl + Bev n = 65) baseline characteristics were balanced; median age was 57 years; 43.4% had Karnofsky performance status 90-100%; 87.6% had measurable disease at baseline. Median number of bevacizumab cycles: 5 for Ona + Bev, 6 for Pl + Bev; median onartuzumab cycles, 4; median placebo cycles, 6. Grade ≥3 adverse events (AEs) were reported in 38.5% of Ona + Bev and 35.9% of Pl + Bev patients; serious AEs were reported in 30.8% and 29.7%, respectively. Grade 5 AEs: Ona + Bev n = 2 intestinal perforation; Pl + Bev n = 1 intracranial hemorrhage. AEs leading to study drug withdrawal were seen in 10.8% of Ona + Bev and 6.3% of Pl + Bev patients. AEs (all grades) with a difference in incidence of ≥10% between arms included peripheral edema (44.6% Ona + Bev, 14.1% Pl + Bev), hypertension (12.3% Ona + Bev, 32.8% Pl + Bev) and hypoalbuminemia (12.3% Ona + Bev, 1.6% Pl + Bev). Efficacy data are pending. CONCLUSION: The AEs observed were consistent with previous safety profiles for onartuzumab and bevacizumab with no new safety signals. Efficacy data will be presented.