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

NCT06389591 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 202301957R37CA251978OCR44973
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in adult patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma

Keywords

brain tumor; malignant brain tumor; immunotherapy; adult

Outcome Measures

Primary Outcomes (2)

• Percentage of vaccines meeting release criteria in the DLT window during the first three vaccines

  Manufacturing feasibility will be determined based on the percentage of vaccines that are successfully manufactured in the DLT window during the first three vaccines. If two-thirds of vaccines are successfully manufactured with Qa/Qc clearance, the investigators will conclude that RNA-LPs can be successfully manufactured.

  from the date of surgery until administration of third vaccine, up to 20 weeks

• Incidence of investigational treatment related toxicities

  AEs and SAEs must be reported begins at time of first investigational product is received and ends 30 days after last investigational product is given.

  from first vaccine to 30 days after last dose of vaccine administered, up to 17 months

Study Arms (1)

Arm 1: pp65 RNA-LPs (DP1) before biopsy

EXPERIMENTAL

Participants will receive pp65 RNA-LPs (DP1) starting before tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Biological: pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1); Biological: RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2)

Interventions

pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1) BIOLOGICAL

pp65 RNA loaded lipid particles or pp65 RNA-LPs administered intravenously

Arm 1: pp65 RNA-LPs (DP1) before biopsy

RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2) BIOLOGICAL

personalized tumor mRNA, pp65 fl LAMP mRNA and DOTAP liposomes or RNA loaded lipid particles, RNA-LPs administered intravenously

Arm 1: pp65 RNA-LPs (DP1) before biopsy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients who received prior treatment with bevacizumab.
• Known active infection (requiring treatment by antiviral or antibiotics) or immunosuppressive disease.
• Patients with multifocal recurrent disease characterized by more than one enhancing lesion separated by noncontiguous T2/FLAIR signal abnormality. Patients with recurrence outside of the original tumor site are eligible if there is stability at the original site of disease.
• Patients with uncontrolled seizure disorders
• Any patients that have received any live vaccines within 30 days prior to enrollment
• Tumors with primary localization to the brainstem or spinal cord
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization.
• Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.
• Acute bacterial or fungal infection requiring intravenous treatment at study treatment.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at study treatment
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Patients with autoimmune disease requiring medical management with immunosuppressants.
• Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.

Sponsors & Collaborators

• University of Florida: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UF Health

Gainesville, Florida, 32608, United States

Location

Related Publications (2)

• Carrera-Justiz S, Aghaee M, Qdaisat S, Weidert F, Garcia GA, Fagman L, Zhang D, Stover B, Moor RSF, Xie C, Goldenberg E, von Roemeling C, Doonan B, Chardon-Robles J, Elliott L, Sawyer WG, Deleyrolle LP, Sahay B, Foster TP, Seligson ND, Rahman M, Ghiaseddin A, Castillo P, Lee JH, Silver NL, Doty A, Ligon JA, Milner RJ, Mitchell D, Mendez-Gomez H, Moore H, Sayour EJ. Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors. J Immunother Cancer. 2025 Nov 11;13(11):e011817. doi: 10.1136/jitc-2025-011817.

  PMID: 41218853 DERIVED

• Villanueva MT. RNA delivery heats up cold tumours. Nat Rev Drug Discov. 2024 Jul;23(7):497. doi: 10.1038/d41573-024-00098-0. No abstract available.

  PMID: 38858569 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ashley Ghiaseddin, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: December 2, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)