AT-21 FINAL RESULTS OF A PHASE 1 TRIAL OF AN ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) AGAINST RECURRENT GLIOBLASTOMA (GBM)

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. We report results of a phase 1 trial evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED). METHODS: Eligible patients were adults with recurrent supratentorial GBM; solitary tumor 1-5cm in diameter; greater than or equal to 4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS > 70%; and positive anti-polio titer. The original two-step continual reassessment method dose escalation was amended to treat 6 patients at level 2 after observing prolonged steroid use in 5 of 7 patients treated on levels 3 to 5. RESULTS: Thus far, 13 patients have been treated (1 each levels 1 and 3, 5 level 2, 2 level 4, 4 level 5). One dose limiting toxicity was observed, grade 4 intracranial hemorrhage at catheter removal (level 5). Adverse events possibly related to study include: hemiparesis (grade 3, n = 3; grade 2, n = 1; grade 1, n = 1); lymphopenia (grade 3, n = 1); seizure (grade 3, n = 1; grade 2, n = 1; grade 1, n = 2); dysphasia (grade 2, n = 1; grade 1, n = 1); lethargy (grade 1, n = 4); headache (grade 2, n = 1; grade 1, n = 2); one each of grade 2 diarrhea, paresthesia and hyperbilirubinemia; and one each of grade 1 fever, cough, nasal congestion, memory impairment, thrombocytopenia, anemia, nausea and vomiting. Ten patients remain alive, with pts #1 and #2 now 25 and 24 months post-PVSRIPO, respectively. Patients on levels 3 to 5 requiring prolonged steroid use were initiated on bevacizumab, allowing tapering down steroids. CONCLUSION: Infusion of PVSRIPO via CED is safe thus far and encouraging efficacy results are observed. Enrollment will be completed for the meeting.