RE:RE:bioMedical Journal-the Lancet-2024 - Glioblastoma vaccinesThe difference between then and now is that the FDA has since expanded the opportunity for biologics by enhancing the Accelerated Approval for biologics in rare/orphan diseases. What also changed towards the effective use of pelareorep in combination with immune checkpoint inhibitors (ICI) is the sequencing-in of pelareop before the administration of an ICI, so that pelareorep is able to "prime" the immune system, and has the time to remodel the TME, in advance of the addition of a checkpoint inhibitor.
In 2014/15 the neoadjuvant treatment of muscle-invasive bladder cancer and the treatment of glioblastoma, had pelareorep being administered intratumorally and without a checkpoint inhibitor.
From what we know now, there was no rational reason to have run a Phase 3 clinical trial in these two indications using pelareorep as a monotherapy being administered intratumorally.
ONCY went on to run a subsequent clinical trial in 2018 that showed that intravenous delivery of reovirus to brain cancer patients immunologically primed the immune system for susequent checkpoint blockade.
https://www.science.org/doi/10.1126/scitranslmed.aam7577
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276984/