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Phase I study of the intratumoral administration of an oncolytic polio/rhinovirus recombinant (PVSRIPO) in recurrent glioblastoma (GBM).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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 a phase I study evaluating the intratumoral convection-enhanced delivery (CED) of PVSRIPO. Methods: Eligibility criteria for adult patients (pts) 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 pt each on dose levels 1-4, and up to 21 pts at dose level 5. Results: Thus far, 10 pts 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 (pt #8) was observed at level 5, a grade 4 intracranial hemorrhage at the time of catheter removal, which required de-escalation to level 4. Adverse events possibly related to study include: hemiparesis (grade 3, n=1; grade 2, n=1; grade 1, n=1); lymphopenia (grade 3, n=1); seizure (grade 2, n=1; grade 1, n=2); lethargy (grade 1, n=4); headache (grade 1, n=2); one each of grade 2 diarrhea, paresthesia, dysphasia and hyperbilirubinemia; and one each of grade 1 fever, cough, nasal congestion, memory impairment, thrombocytopenia, anemia, nausea and vomiting. Eight pts remain alive, with pts #1 and #2 now 20 and 19 months post PVSRIPO, respectively. Two BEV failure pts died six months post-infusion after initiating hospice care due to persistence of baseline neurologic limitations. After observing prolonged steroid use in 5 of 7 pts treated on dose levels 3 to 5 and considering the clinical effects of the complex host inflammatory response to viral tumor infection, 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 pts at dose level 2. Conclusion: Infusion of PVSRIPO via CED is safe thus far and observed efficacy outcomes are intriguing. Clinical trial information: 01491893.
Abstracts by Annick Desjardins:
- Meeting: 2016 ASCO Annual Meeting | Abstract No: 10125
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.Meeting: 2016 ASCO Annual Meeting | Abstract No: 2061
Phase 1, multicenter, open-label, dose-escalation, study of marizomib (MRZ) and bevacizumab (BEV) in WHO grade IV malignant glioma (G4 MG).Meeting: 2016 ASCO Annual Meeting | Abstract No: 2037