RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)

Inclusion Criteria26

• Age >/= 18years
• Histopathologically proven GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).
• Unequivocal evidence of tumor progression as documented by brain MRI scan per RANO criteria.
• Tumor must have a primary supratentorial component at the time of disease progression.
• Patients must have received surgery and completed Fractionated Radiation therapy as frontline treatment for primary disease, either alone or with concurrent therapy (including temozolomide or another systemic chemotherapy agent). Patients must be at least 12 weeks post chemoradiation completion.
• Patient must be at least 90 days from completion of prior radiation
• Any adverse events patient has experienced from prior therapy must have resolved to ≤ Gr. 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) v5.0 prior to enrollment
• Patient must be either weaned off steroids or weaned onto physiologic dosing at the time of enrollment.
• Patient must be a candidate for surgery/biopsy as acceptable standard of care for sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).
• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.
• Performance Score: (KPS) ≥ 60. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Bone Marrow:
• ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported)
• Platelets ≥ 100/µl (unsupported for at least 3 days)
• Hemoglobin > 8 g/dL
• Renal:
• BUN ≤ 25 mg/dl
• Creatinine ≤ 1.7 mg/dl
• Hepatic
• Bilirubin ≤ 2.0 mg/dl
• ALT ≤ 5 times institutional upper limits of normal for age
• AST ≤ 5 times institutional upper limits of normal for age
• Patient must be able to give consent.
• For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment.
• WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
• Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.