Update on Recombinant Poliovirus Cancer Immunotherapy
The Phase-2 study of PVSRIPO in recurrent glioblastoma, combined with an immune checkpoint inhibitor (pembrolizumab), is now active and recruiting patients at Duke (NC), Jacksonville Baptist (FL), University Hospitals Cleveland (OH), with other sites at Oregon Health (OR), Ohio State (OH), Harvard Dana Farber/Mass General/Beth Israel (MA), Univ. of Connecticut (CT), and Univ. of California San Francisco (CA) coming on board.
Our promising Phase-1 study of PVSRIPO (alone) in recurrent, nonresectable melanoma was just published (https://jitc.bmj.com/content/9/4/e002203). Out of 12 patients, 4 achieved confirmed partial (2) or complete (2) responses with durable cancer control currently >19 months after the last dose of PVSRIPO.
Based on our Phase-1 data in recurrent, nonresectable melanoma, a Phase-2 clinical trial has opened of PVSRIPO (+ pembrolizumab) at multiple leading institutions in the US: Univ. of Kentucky, Louisville (KY), Henry Ford Hospital, Detroit (MI), Univ. of Pittsburgh (PA) with at least 18 additional sites scheduled to join the study. The 1st patient has been treated, and a busy pipeline of patients is coming onto the study.
We received permission from the FDA to start our exciting clinical protocol in muscle-invasive bladder cancer (MIBC). MIBC is bladder cancer that has progressed and invaded the muscle layer surrounding the bladder; there is currently no effective therapy. PVSRIPO will be administered (+ pembrolizumab) in 3 doses before surgery (for patients without metastatic disease) or without surgery (in patients where surgery no longer is an option due to the presence of metastases). The leading experts will conduct this immunotherapy trial in bladder cancer across the country (at the University. of California San Francisco, New York University, UNC Chapel Hill, and Duke). If successful, this treatment paradigm could be expanded to many patients with diverse cancers before surgical removal.
The highlight of the past research year was a pivotal publication from Michael Brown in my lab, who deciphered the precise mechanism of how PVSRIPO instigates “tumor antigen-specific antitumor CD8+T cell immunity”: https://www.nature.com/articles/s41467-021-22088-1.