NCT05660408

RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

RNA PRIME - RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 3 Years – 39 Years
• Healthy volunteers: Not accepted

Summary

The Investigators have demonstrated in preclinical studies that RNA liposomes activate APCs, induce antigen-specific T cell immunity, and can supplant DCs in a cell therapy model for HGG and have shown feasibility and activity of this approach in preclinical models and in canine patients with a spontaneous malignant glioma. In one arm of this study, we will investigate the safety and immunologic activity of RNA-LP vaccines in pediatric patients with recurrent pHGG. The investigators have also shown that intravenous administration of tumor mRNA loaded lipid particles (LPs) localizes primarily to lung, transfect antigen presenting cells (APCs) and lead to an activated T cell response for induction of anti-tumor immunity. In contrast to other formulations, RNA-LPs recruit multiple arms of the immune system (i.e. innate/adaptive), and remodel the systemic/intratumoral immune milieu, which remain potent barriers for vaccine, cellular, and checkpoint inhibiting immunotherapies. After only a single RNA-LP vaccine, the bulk of systemic and intratumoral dendritic cells (DCs) in mice display an activated phenotype; these activated DCs (harvested from tumors) expand antigen specific T cell immunity. In immunologically resistant pulmonary osteosacroma murine tumor models (i.e. K7M2), RNA-LPs induce robust anti-tumor efficacy in settings where immune checkpoint inhibitors (i.e. anti-PD-L1 therapy) do not confer therapeutic benefit. The investigators have already demonstrated safety of RNA-LPs in acute/chronic murine toxicity studies, and in client-owned canine trial. In this study, we will investigate the manufacturing feasibility, safety and immunologic activity of RNA-LP vaccine in patients with recurrent pulmonary or unresectable osteosarcoma and recurrent pHGG.

Detailed description

For recurrent pHGG there will be two non-randomized arms assigned at the discretion of the patient and treatment team: * Arm 1-A single neoadjuvant pp65 RNA-LP (DP1) will be administered prior to surgical resection/biopsy, and then two adjuvant DP1. * Arm 2-Surgical resection/biopsy will occur first and all three DP1 will be administered in the adjuvant setting For recurrent OSA there will be three arms based on disease status on enrollment: * Arm 1-Patients with unilateral pulmonary-only metastatic recurrent OSA * Arm 2-Patients with bilateral pulmonary-only metastatic recurrent OSA * Arm 3-Patients with unresectable OSA in any location. The Phase I dose-escalation study for either recurrent/progressive pHGG or recurrent OSA cohort will be performed in 18 subjects using a 3+3 design. Both recurrent pHGG trial arms will be enrolled together as a single cohort for safety, and similarly all recurrent OSA trial arms will be enrolled together as a single cohort for safety during phase I.

Conditions

• Recurrent Pulmonary Osteosarcoma
• Recurrent High-grade Glioma

Interventions

Type	Name	Description
BIOLOGICAL	pp65 RNA LP (DP1)	This is an off the shelf RNA-LP vaccine used to prime for the immune response while we produce the patient specific pp65/tumor mRNA RNA-LP (DP2)
BIOLOGICAL	pp65/tumor mRNA RNA-LP (DP2)	This is a patient specific RNA-LP vaccine generated from the patient's tumor RNA.
PROCEDURE	Surgical Biopsy/Resection	Eligible participants will be enrolled and undergo sterile collection of tumor material .

Timeline

• Start date: 2025-03-12
• Primary completion: 2033-10-01
• Completion: 2035-10-01
• First posted: 2022-12-21
• Last updated: 2026-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study