Patient survival on the dose escalation phase of the Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG) clinical trial compared to historical controls.

Background: The live attenuated oral (SABIN) serotype 1 poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report the survival results of the dose-finding portion evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED) compared to a historical control group of patients (pts) treated at Duke. Methods: Eligible pts on trial were adults with recurrent supratentorial WHO grade IV MG; solitary tumor 1-5cm in diameter; ≥ 4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS ≥ 70%; and positive anti-polio titer. A historical group of adult recurrent WHO grade IV mg pts treated at Duke between 1/01/07-12/15/14 was retrospectively identified based on presence of a solitary tumor 1-5cm in diameter, KPS ≥ 70%, and absence of clinical decline which would have prevented enrollment on the PVSRIPO trial. Results: Fifteen pts were treated in the dose escalation phase, dose levels 1-5 (1 each at dose levels 1 and 3, 7 at level 2, 2 at level 4, and 4 at level 5), while 124 pts were identified as historical controls. Patient characteristics were similar for age, gender, KPS, prior number of progressions, steroid dosage at enrollment, and prior bevacizumab failure; however, 80% of PVSRIPO pts versus 58.9% of control pts had a gross total resection at diagnosis. As of 1/15/16, a median OS of 12.6 months was observed for the PVSRIPO group versus 10.5 months for the historical controls, with 23.3% of PVSRIPO pts alive at 24 months versus 13.7% of historical controls. Conclusions: Infusion of PVSRIPO via CED seems to have a survival advantage when compared to historical control pts treated at the same institution, with a higher proportion of patients alive at 24 months. Reported pts were not treated at what was identified as the optimal dose of PVSRIPO (dose level -1). It is predicted that the pts treated at the optimal dose will have a greater increase in survival. Clinical trial

Duke Scholars

Author John Howard Sampson Neurosurgery

Author Katherine Barnett Peters Neurosurgery, Neuro-Oncology

Author James Emmett Herndon II Biostatistics & Bioinformatics, Division of Biostatistics

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology

Author Darell Doty Bigner Neurosurgery

Author Matthias Gromeier Neurosurgery, Neuro-Oncology