Top-line results from the pivotal Phase 3 GLOBE study of ofranergene obadenovec in combination with bevacizumab in patients with recurrent glioblastoma were reported today, and the study did not meet its primary endpoint of overall survival.
Top-line results from the pivotal Phase 3 GLOBE study of ofranergene obadenovec (VB-111) in combination with bevacizumab (Avastin) in patients with recurrent glioblastoma (rGBM) were reported today, and the study did not meet its primary endpoint of overall survival (OS).
The GLOBE Phase 3 trial is a randomized, controlled, double-arm, open-label study of the potential first-in-class anticancer therapeutic candidate ofranergene obadenovec, dosed once every other month with bevacizumab every other week. The combination therapy was compared to bevamcizumab as a monotherapy.
Ofranergene obadenovec has exhibited statistically significant OS and progression-free survival (PFS) in a Phase 2 trial in patients with rGBM, compared to the current standard of care, and the drug has received orphan drug designation in both the U.S. and Europe. It has also been granted fast track designation by the U.S. Food and Drug Administration (FDA) for prolongation of survival in patients with rGBM.
"We are disappointed that our encouraging Phase 2 data were not replicated in the GLOBE Phase 3 study, and once we receive the full and final data we will be analyzing them carefully to better understand the outcome of the study,” Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics in a press release. “We are grateful to the trial investigators, site personnel, patients and caregivers who participated in GLOBE. We believe that VB-111 may still hold promise for other indications we currently or may study in the future.”
Key inclusion criteria in the the study include first or second progression of GBM following standard of care treatment with temozolomide and radiation, a histologically confirmed diagnosis of glioblastoma and measurable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria at progression, which is used to assess response to first-line treatment in patients.
GBM presents via headaches, changes in personality, nausea, and stroke-like symptoms. It can be caused by a genetic disorder like neurofibromatosis or the result of prior radiation therapy. According to the Mayo Clinic, the disease can be incredibly difficult to treat, and current standard of care consists mainly of therapies that slow the progression of cancer and alleviate signs and symptoms.
In the video below from the Rare Disease Report Insights series, Susan C. Pannullo, M.D. of the Weill Cornell Brain and Spine Center; and Steven A. Toms, M.D. of the Geisinger Health System discuss the current treatment options in rGBM: