This is a first in human Phase I study of RNA-LP vaccines for newly diagnosed adult MGMT unmethylated glioblastoma (GBM). The phase I portion of the study will involve a dose-escalation study to identify the maximally tolerated dose (MTD). Up to 28 participants may be enrolled.~This clinical trial will consist of three parts: Surgery, Radiation, and Immunotherapy. Surgery and chemoradiation will be standard of care for patients with GBM. Potentially eligible participants will be enrolled on a screening consent for the sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs). Tumor material will be sent to the University of Florida (UF). Following surgical resection with confirmatory pathologic diagnosis, patients will be enrolled in the trial after informed consent has been obtained.~The RNA-LP vaccination will begin within 4 weeks following radiation and after review of post-radiation MRI (for baseline). After radiation patients will receive three RNA-LP vaccines every 2 weeks before beginning 12 cycles of adjuvant monthly RNA- LP vaccines for a total of 15 vaccines.~Participants may receive RNA-LP vaccines for up to 14 months.~Participants will be followed until death due to any cause. MRI and clinical evaluation for assessment of disease progression will be conducted every 3 months for the first year post-immunotherapy and then every 6-12 months over the next 2 years.
The primary objective will be to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in (Stratum 1) adult patients with newly diagnosed GBM (MGMT unmethylated). Funding Source - FDA OOPD