ATIM-19. RESULTS OF THE GLOBE STUDY: A PHASE 3, RANDOMIZED, CONTROLLED, DOUBLE-ARM, OPEN-LABEL, MULTI-CENTER STUDY OF VB-111 COMBINED WITH BEVACIZUMAB VS. BEVACIZUMAB MONOTHERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA

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Ofranergene obadenovec (VB-111) is a viral cancer-therapy with a dual mechanism: vascular disruption and induction of a tumor directed immune response. In a phase 2 trial, recurrent GBM (rGBM) patients treated with VB-111, followed at progression with VB-111 in combination with bevacizumab (BEV), had durable tumor growth attenuation, associated with prolonged overall survival (OS) of 15 months. A phase 3 multisite international randomized open-labeled controlled trial. Patients with rGBM were randomized 1:1 to receive VB-111 at 10e13VPs q8W in combination with BEV 10mg/Kg q2W vs. BEV 10mg/Kg q2W. Primary endpoint was OS. 256 patients (128 per arm) were enrolled in 57 sites. The mean age was 55, 67% were male. 74% were in 1st progression, KPS < 80 found in 23% of patients. In the combination arm vs the BEV arm: baseline tumor volume > = 15cm3 in 49% vs 41%; Grade 3–4 adverse events reported among 61 % (mostly CNS and febrile) vs 34%, and pyrexia in 39% vs 4% of patients; ORR was 27.3% vs 21.9% and median duration of response was 3.7 vs 2.2 months. Median OS was 6.8 vs 7.9 months in the combination vs BEV arms, HR 1.2 [95% CI 0.910–1.59, p=NS]. In the subgroup of patients with baseline tumors< 15 cm3, OS was 9.2 vs 8.3 months [p=NS], and 12 month OS was 38.9% vs 26.9% [p=NS]. Among patients in the combination arm, OS was 7.9 vs 5.5 in patients with and without a febrile reaction. In this trial, VB-111 in combination with BEV failed to increase OS in patients with rGBM. Lack of VB-111 priming, as done in the phase II trial may explain the differences with the favorable outcomes in the latter. Patients with large progressive tumors may precluded sufficient drug exposure. Additional exploratory analyses are ongoing.

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