On January 8, 2020 VBL Therapeutics (Nasdaq: VBLT) reported the publication of clinical data from the Phase 2 and Phase 3 studies of VB-111 (ofranergene obadenovec) in recurrent glioblastoma (rGBM) in two manuscripts published in the peer-reviewed journal Neuro-Oncology, the official journal of the Society for Neuro-Oncology (Press release, VBL Therapeutics, JAN 8, 2020, View Source [SID1234552857]).

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In the Phase 2 study, patients with rGBM who were primed with VB-111 monotherapy that was continued after progression with the addition of bevacizumab (Avastin) showed significant survival (414 vs 223 days; HR 0.48; p=0.043) and progression free survival (PFS) advantage (90 vs 60 days; HR 0.36; p=0.032) compared to a cohort of patients that had limited exposure to VB-111 (see manuscript by Brenner et al). Radiographic responders to VB-111 exhibited specific imaging characteristics related to its mechanism of action. Survival advantage was also seen in comparison to historic controls, with the percentage of patients living more than one year doubling from 24% to 57%.

The GLOBE Phase 3 study, top-line data from which were announced in 2018, compared upfront concomitant administration of VB-111, without priming, and bevacizumab to bevacizumab monotherapy. In this modified regimen, the treatment did not improve overall survival (OS) and PFS outcomes in rGBM. The new manuscript by Cloughesy et al. attributes the contradictory outcomes between the Phase 2 and Phase 3 trials as being related to the lack of VB-111 monotherapy priming in the GLOBE study, providing clinical, mechanistic and radiographic support for this hypothesis. Notably, GLOBE data show improved outcomes associated with a post VB-111 fever reaction, similar to outcomes from previous VB-111 studies, providing further support that fever is a potential biomarker for better survival with VB-111, secondary to the drug’s immunologic mechanism of action.

"The emerging picture from the Phase 2 and Phase 3 trials points to study regimen as a key factor for ofranergene obadenovec efficacy in rGBM," said Patrick Wen, M.D., Director, Center for Neuro-Oncology at Dana-Farber Cancer Institute, Boston, MA, and a key investigator in both clinical trials. "These results warrant further assessment of ofranergene obadenovec, which we intend to advance in a new randomized, controlled, clinical trial in patients with rGBM undergoing a second surgery."

Details on the new investigator-sponsored Phase 2 trial of VB-111 in rGBM were recently presented at the 2019 Society for Neuro-Oncology Annual Meeting (see link). An investigational new drug application for the new study has already gone into effect with the FDA and study launch is expected in early 2020. VB-111 is also being investigated in a Phase 3 pivotal study in ovarian cancer with interim data expected in the first quarter of 2020.

For a link to the newly published VB-111 papers in Neuro-Oncology refer to: Phase 2 manuscript and Phase 3 manuscript.