Abstract CT416: Intratumoral administration of an Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in recurrent glioblastoma (GBM): Preliminary results of the Phase I clinical trial

Abstract

Abstract Background: PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site stemming from human rhinovirus type 2. An oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy, nectin-like molecule-5, is recognized by PVSRIPO. We report the preliminary results of a phase I clinical trial evaluating the intratumoral administration via convection-enhanced delivery (CED) of PVSRIPO. Methods: Eligibility criteria for adult patients included: recurrent supratentorial GBM; 1-5 cm in diameter; ≥1cm away from the ventricles; ≥4 weeks after chemotherapy, bevacizumab (BEV) or study drug; adequate organ function; KPS >70%; and positive anti-poliovirus titer. Dose was rapidly escalated using a two-step continual reassessment method with anticipated accrual of 1 patient each on dose levels 1-4, and up to 21 patients at dose level 5. Results: Thus far, ten patients have been treated (1 each at levels 1 and 3, 2 at level 2, 2 at level 4, 4 at level 5). One dose limiting toxicity (patient #8) was observed at level 5, a grade 4 intracranial hemorrhage at the time of catheter removal, which required de-escalation to level 4. Grade 3 adverse events possibly related to study include hemiparesis (n=1) and lymphopenia (n=1). No grade 5 study related adverse events were observed. Eight patients remain alive, with two patients now 20 and 19 months post PVSRIPO, respectively. Two patients having previously failed BEV died six months post-infusion after initiating hospice care due to persistence of baseline neurologic deficits. After observing prolonged steroid use in 5 of 7 patients treated on dose levels 3 to 5 and after results of new immunogenic analysis became available, it was agreed upon that dose level 2 is probably the optimal dose level. The study has been amended to treat a total of 6 patients at dose level 2. Conclusion: Infusion of PVSRIPO via CED in the clinical setting is safe thus far and observed efficacy outcomes are intriguing. Dose expansion at dose level 2 is ongoing. Citation Format: Annick Desjardins, J H. Sampson, K B. Peters, T Ranjan, G Vlahovic, S Threatt, J E. Herndon, S Boulton, D Lally-Goss, F McSherry, A Friedman, H S. Friedman, D D. Bigner, M Gromeier. Intratumoral administration of an Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in recurrent glioblastoma (GBM): Preliminary results of the Phase I clinical trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT416. doi:10.1158/1538-7445.AM2014-CT416