Abstract Background Patients with relapsed CNS and extracranial solid tumors have few effective therapeutic options. T cells can be endogenously activated using cancer vaccines, but these vaccines must induce rapid immunologic response against continually evolving malignancies and have not yet been particularly effective for CNS tumors. We developed a multi-lamellar RNA lipid nanoparticle aggregate (RNA-LPA) incorporating autologous total tumor RNA as a novel personalized immunotherapeutic. In the first-in-human clinical trial for adults with glioblastoma, we demonstrated the capacity for this novel RNA therapeutic to generate a profound immunologic response against tumor specific antigens with evidence of significant T cell infiltration into resected tumor. Methods RNA PRIME is a “basket trial” to treat multiple types of recurrent pediatric CNS and solid tumors. The initial CNS arm is a first in pediatric Phase I trial for patients with recurrent pHGG. The primary objective will be to demonstrate the manufacturing feasibility, safety, and to determine the MTD of RNA-LPAs in patients with recurrent/progressive pHGG. Major eligibility criteria include age 3-25 years; evidence of recurrent high-grade glioma, able to have surgical resection at enrolling institution and functional status at time of enrollment of 60%. Brainstem tumors are excluded. Patients will receive RNA-LPA starting either before or after standard-of-care tumor biopsy/resection. Both arms of the recurrent/progressive pHGG component of this clinical trial will consist of two phases: 1) pp65 RNA-LPA (DP1) phase and 2) pp65/tumor mRNA RNA-LPA (DP2) phase, with vaccine administration spacing from an initial bi-weekly to monthly for one year. Correlative studies include peripheral immune monitoring, tumor microenvironment, ex vivo tumor modeling and gut microbiome of patients receiving RNA-LPs. Total accrual target is 18 subjects. Additional arms of RNA PRIME currently include an arm for patients with recurrent/progressive osteosarcoma, and future arms are anticipated for additional CNS and extracranial malignancies.
Hodik et al. (Fri,) studied this question.