Introduction: Current therapies for glioblastoma are limited by ineffective delivery beyond the blood-brain barrier, limited diffusion of regionally-delivered macromolecules, and lack of tumor specificity. Sustained direct intracerebral infusion at slow flow rates [convection-enhanced delivery (CED)] can overcome delivery barriers. 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 are reporting results of an ongoing phase I study evaluating PVSRIPO via CED delivery.
Methods: Adult patient eligibility: 1-5 cm of measurable supratentorial recurrent glioblastoma >=1cm away from the ventricles; >=4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS >=70%; and positive anti-poliovirus titer. PVSRIPO is delivered intratumorally by CED over 6.5 hours. PVSRIPO dose escalation is accomplished by increasing agent concentration, allowing flow-rate and infusion volume to remain constant. A two-step continual reassessment method is used for dose escalation, with 1 patient each treated on dose levels 1-4, and a possibility of <=13 patients on dose level 5.
Results: Total of 6 patients have been treated. Two grade 3 adverse events were observed. Median PFS is 4.0 months (95% CI: 0.9, 'infinity'); median OS not estimable. Six-month PFS is 41.7% (95% CI: 5.6%, 76.7%); 6-month OS is 66.7% (95% CI: 5.4%, 94.5%). Patient #1 failed bevacizumab prior to enrollment and remains disease free more than 9 months post PVSRIPO. Two patients are disease free 8+ and 2+ months post treatment, respectively. One had pathology confirmed disease recurrence 2 months post treatment and 1 came off study due to clinical decline 4 months post treatment.
Conclusions: PVSRIPO infusion via CED is safe thus far with encouraging efficacy results. Updated results will be presented at the meeting.
Patient Care: Shows the efficacy of a drug delivery method that overcomes delivery barriers and has greater tumor specificity.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the use and value of convection-enhanced delivery, 2) Understand the impact of overcoming delivery barriers and having greater tumor specificity