Abstract
Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vasculature. The response to bevacizumab is transient and short-lived after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor cell lysates. The proposed action of ERC1671 is the stimulation of the patients’ immune system. This ongoing phase 2 study has a goal to determine the safety and effectiveness of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab for recurrent GBM. ERC1671/GM-CSF is intradermally administered 2-3 times a week and for five total into maximum 18 days, while cyclophosphamide is orally administered for 4 days at the beginning. GM-CSF dose is 250 µg/m2 and cyclophosphamide dose is 50 mg/day. Bevacizumab is administered as standard of care at 10 mg/kg every 2 weeks. The treatment cycle is 28 days. 9 recurrent bevacizumab-naïve GBM patients, with KPS higher than 70, were treated with ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab v. Placebo + Bevacizumab. Median age was 59 (48-74), with 2 patients being female, and the average KPS 80 (70-100). These patients were unblinded at the time of further progression – 4 received vaccine, 4 received placebo, and 1 was non-evaluable due to discontinuation prior to completion of 1 cycle. Overall survival of patients treated with ERC1671 + Bevacizumab was more than 513 days, compared to patients treated with Placebo + Bevacizumab was 213 days (p=0.048). First clinical results for toxicity show an equal distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs. The addition of ERC1671/GM-CSF/Cyclophosphamide to bevacizumab for recurrent glioblastoma resulted in a clinically meaningful survival benefit with minimal additional toxicity. The phase 2 randomized, double-blinded study is ongoing with anticipated 2 subsites.