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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. PVSRIPO recognizes nectin-like molecule-5, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. Within, we report on the ongoing phase I study evaluating the intratumoral convection-enhanced delivery (CED) of PVSRIPO. METHODS: Eligibility criteria for adult patients with recurrent supratentorial GBM included: 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 2 and higher adverse events possibly related to study include: hemiparesis (grade 3, n = 1; grade 2, n = 1); lymphopenia (grade 3, n = 1); seizure (grade 2, n = 1); and one each of grade 2 diarrhea, paresthesia, dysphasia and hyperbilirubinemia. To date, 8 out of 10 patients are alive, with patients #1 and #2 now 20 and 19 months post PVSRIPO, respectively. Two BEV failure patients died six months post-infusion after hospice care was initiated due to persistence of baseline neurologic limitations. 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. To date, the original study design has been amended to treat a total of 6 patients at dose level 2. CONCLUSIONS: Infusion of PVSRIPO via CED is safe thus far and observed efficacy outcomes are intriguing and warrant further clinical investigation. SECONDARY CATEGORY: Immunobiology & Immunotherapy.

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