Dose finding study of the intratumoral administration of the oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG).

Abstract

e13533 Background: The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report results of the dose finding trial evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED). Methods: Eligible patients were adults with recurrent supratentorial WHO grade IV MG; solitary tumor 1-5.5cm in diameter; ≥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 decrease to dose level(DL) -1 and DL -2 after observing prolonged steroid use in patients treated on higher DLs. Results: As of 2/01/2017, 52 pts were treated on study (1 each at DL1 and DL3, 7 at DL2, 2 at DL4, 4 at DL5, 24 at DL -1 and 13 at DL -2). Only one DLT was observed, a grade 4 intracranial hemorrhage at the time of catheter removal on DL5. Grade 3 or higher adverse events possibly, probably or definitely related to PVSRIPO include: lymphopenia (grade 3, n = 1), steroid myopathy (grade 3, n = 1), cerebral edema (grade 4, n = 1), headache (grade 3, n = 1), dystonia (grade 3, n = 1), pyramidal tract syndrome (grade 3, n = 6), seizure (grade 3, n = 1; grade 4, n = 1), delusions (grade 3, n = 1), hypertension (grade 3, n = 1), and thromboembolic events (grade 3, n = 2). At a median follow-up of 20.1 months, 20.8% of pts remain alive at 36-month post PVSRIPO infusion, compared to 4% of an historical control. Four pts remain alive more than 22 months post treatment without having received any additional intervention following PVSRIPO at 57.5+, 56.4+, 27.9+ and 23.2+ months. Conclusions: Infusion of PVSRIPO via CED is safe and encouraging efficacy results are observed. The dose finding study is now completed and we are initiating clinical trials evaluating combination of PVSRIPO with other therapies. Clinical trial information: NCT01491893.