===
Glioblastoma Trials ===
Adult A
Phase 1 clinical trial published in the
New England Journal of Medicine in 2018 enrolled 61 patients with recurrent
glioblastoma between 2012 and 2017, with overall survival at 24 and 36 months reaching 21%, compared to 14% at 24 months and 4% at 36 months in matched historical controls. Istari Oncology initiated the LUMINOS-101
Phase 2 trial, investigating PVSRIPO in combination with
pembrolizumab in patients with recurrent glioblastoma, testing whether the combination enhances antitumor immune responses.
Children A Phase 1b safety study published in 2023 assessed PVSRIPO delivery directly into brain tumors of pediatric patients with recurring high-grade glioma. The trial enrolled eight patients between ages 4 and 21, each receiving one intratumoral infusion. Treatment was well tolerated, with transient side effects including headaches and seizures in most patients. None experienced lasting severe complications or died from treatment effects. Several patients needed
bevacizumab to manage brain swelling around the tumor site. Patient survival averaged approximately four months, though one participant lived beyond 22 months. Researchers concluded the delivery method showed acceptable safety for advancement to further testing in young patients. ===
Melanoma Trials === A Phase 1 trial in patients with unresectable, treatment-resistant melanoma who had progressed on
anti-PD-1 therapy demonstrated antitumor activity, with 4 of 12 patients achieving confirmed responses and durable control in some cases.The virus was injected directly into tumors and caused minimal side effects. Four patients showed tumor shrinkage or complete disappearance, with disease control lasting over 19 months in some cases. In 2021, the
FDA granted
Fast Track designation and
Orphan Drug Designation to PVSRIPO for the treatment of advanced melanoma in patients with disease progression after
anti-PD-1/anti-PD-L1 therapy. A Phase 2 trial (LUMINOS-102) is testing PVSRIPO both as monotherapy and combined with checkpoint inhibitors in melanoma patients whose disease progressed after initial immunotherapy. ===
Bladder Cancer Trials === PVSRIPO is being investigated in the LUMINOS-103 basket trial, including sub-studies in muscle-invasive and non-muscle-invasive
bladder cancer, with combinations involving
pembrolizumab or monotherapy via
intravesical administration. Clinical trials in
muscle-invasive bladder cancer began following FDA clearance, testing PVSRIPO combined with
pembrolizumab as presurgical treatment or for patients with inoperable
metastatic disease. == Regulatory Designations by
US Food and Drug Administration ==