Neuro-Oncology 16:iii42 – iii52, 2014. doi:10.1093/neuonc/nou209.5
NEURO-ONCOLOGY
Wednesday, July 23, 2014
ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN RECURRENT GLIOBLASTOMA (GBM): FIRST PHASE I CLINICAL TRIAL EVALUATING THE INTRATUMORAL ADMINISTRATION Annick Desjardins, MD, FRCPC, John H. Sampson, Katherine B. Peters, Tulika Ranjan, Gordana Vlahovic, Stevie Threatt, James E. Herndon, II, Susan Boulton, Denise Lally-Goss, Frances McSherry, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, and Matthias Gromeier; Duke University Medical Center
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 ¼ 1; grade 2, n ¼ 1); lymphopenia (grade 3, n ¼ 1); seizure (grade 2, n ¼ 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 postinfusion 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.
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
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