(P 426) A PHASE I/II TRIAL USING RNA LIPID NANOPARTICLES FOR RECURRENT OSTEOSARCOMA: A REPORT FROM THE NATIONAL PEDIATRIC CANCER FOUNDATION

Objective: Recurrent osteosarcoma (rOS) has few effective therapeutic options. We developed multi-lamellar RNA lipid nanoparticles (RNA-LP) incorporating autologous total tumor RNA as a personalized immunotherapeutic to reprogram the tumor microenvironment and target the tumor. Canine studies, including OS, provided preliminary data on safety and efficacy. We designed a first-in-pediatrics clinical trial testing the safety, feasibility, and efficacy of this approach for rOS (NCT05660408).

Methods: RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors (RNA PRIME) is a multi-institutional Phase I/II trial, funded by the National Pediatric Cancer Foundation, NCI, and the V Foundation, designed to test RNA-LP in recurrent pediatric brain tumors and rOS. Phase I follows a 3+3 dose escalation followed by a modified Simon Two-Stage Phase II at the recommended phase II dose. The primary phase I objective is to demonstrate manufacturing feasibility and safety, and the primary phase II objective is 12-month event-free survival for resectable pulmonary rOS and 4-month progression-free survival for unresectable rOS. Main eligibility criteria include: age 3-39 years, ability to undergo surgical resection or biopsy, adequate organ function, and Karnofsky/Lansky performance status ≥60%. The study consists of three parts: 1) biopsy/resection; 2) “off the shelf” pp65 (a CMV-associated viral peptide) RNA-LP administered biweekly, followed by contralateral thoracotomy when indicated; and 3) personalized pp65/tumor mRNA RNA-LP administered biweekly x3 then monthly for up to 1 year. Correlative studies examine peripheral blood and tumor immune monitoring. Accrual began in April 2025. The trial will enroll up to 18 subjects in phase I and up to 55 subjects in phase II . Patients with unilateral or bilateral resectable rOS will be analyzed together while patients with unresectable rOS will be analyzed separately.

Results: N/A

Conclusion: N/A