ATNT-07FAVORABLE RESPONSE OF PATIENTS WITH GLIOBLASTOMA AT SECOND OR THIRD RECURRENCE TO REPEATED INJECTION OF ONCOLYTIC PARVOVIRUS H-1 IN COMBINATION WITH BEVACICUMAB

BACKGROUND: Among various experimental therapies for glioblastoma is the use of oncolytic viruses that specifically target and destroy cancer cells. Parvovirus H-1 (H-1PV), an apathogenic oncolytic rodent DNA virus, is tested in a phase 1/2a trial in patients with recurrent glioblastoma (ParvOryx01 trial, clinical trial identifier NCT01301430). Here we report on a series of 6 patients previously treated in the ParvOryx01 trial who received at another recurrence an additional local dose of H-1PV based on a compassionate use (CU) agreement. METHODS: 6 patients (all male, age 51 to 71 years) developed another tumor recurrence between 4 and 12,6 months (mean: 7,8 months) after treatment with H1PV in the ParvOryx01 trial. All 6 patients underwent tumor resection and injection of 5x108 plaque forming units (pfu) of H-1PV, followed by chemotherapy (n = 1), bevacicumab (n = 5) or no treatment (n = 1). The CU-virus dose was provided by the sponsor (Oryx GmbH&Co KG, Baldham, Germany) on a humanitarian basis. RESULTS: The censored mean survival of all 6 patients at second or third recurrence of GBM after compassionate use of H-1PV was 14,7 months (9 to 26 months). 3 of 6 patients are still alive 9,11 and 26 months after CU. Of 5 patients treated with bevacicumab after CU, 3 showed striking remissions of another tumor recurrence and the censored mean survival for this subgroup is 15,4 months. CU of H-1PV was tolerated without side effects. CONCLUSIONS: Repeated injection of H-1PV as compassionate use treatment in combination with bevacicumab led to longer survival times in patients at second or third recurrence of GBM compared to previous study treatment. This clinical data points to a synergistic effect of bevacicumab and H-1PV in the treatment of malignant gliomas.