This clinical trial is designed to evaluate the safety and efficacy of a universal mRNA vaccine targeting a panel of glioma-associated mutations in patients with recurrent or progressive high-grade glioma.
The primary objectives are to address the following key questions: 1) Is the mRNA vaccine safe for this patient population? 2) Does the vaccine stimulate an anti-tumor immune response and promote tumor regression?
Participants will receive the vaccine according to the following schedule:
1. one injection per week for four consecutive weeks, followed by one injection every four weeks for four cycles, and subsequently, one injection every 12 weeks for maintenance. 2. Safety and efficacy assessments, including detailed recording of adverse events and tumor growth evaluation, will be conducted at follow-up visits scheduled for weeks 6, 12, and months 6, 9, 12, 18, 24, and 36 post-treatment initiation.
Adequate compliance, ability to comprehend the clinical trial, and provision of written informed consent.
Male or female, aged ≥16 years.
Histologically or cytologically confirmed WHO Grade III or IV glioma harboring one or more of the following mutations: H3.3K27M, H3.1K27M, H3.3G34R, BRAF V600E, PIK3CA H1047R, IDH1 R132H, or EGFRvIII.
Recurrent or progressive high-grade glioma, defined as a CNS WHO Grade 3-4 glioma confirmed by post-surgical histopathology, with documented recurrence or progression per RANO criteria on MRI following standard therapy (radiotherapy plus temozolomide chemotherapy).
History of other malignancies within the past 5 years (except appropriately treated carcinoma in situ of the cervix or non-melanoma skin cancer).
History of hypersensitivity to chemotherapy agents or radiosensitizers used for central nervous system or head and neck cancers.
History of severe allergic reactions to vaccines or any components of the investigational product.
Human Immunodeficiency Virus (HIV) antibody
Single group
Glioma-related multi-target mRNA vaccines
Biological/VaccineMulti-targeted mRNA vaccines encoding the following GBM-associated mutations: H3.3K27M, H3.1K27M, H3.3G34R, BRAFV600E, PIK3CAH1047R, IDH1R132H, EGFRvIII
Safety and tolerability of a mRNA vaccine
All adverse events (AEs) treatment, emergent adverse events, treatment related toxici will be recorded. AE severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version \[Specify Version, e.g., 5.0\]. Dose-limiting toxicities (DLTs) are defined as occurring within the DLT observation period \[Specify period, e.g., 28 days after the first dose\] and include: 1. Any CTCAE Grade 4 local injection site reaction. 2. Any CTCAE Grade 3 local injection site reaction persisting for ≥2 weeks despite optimal supportive care. 3. Any hypersensitivity reaction of at least CTCAE Grade 3 severity. 4. CTCAE Grade 4 cerebral edema. 5. Autoimmune reactions of CTCAE Grade 3 or higher. 6. Any CTCAE Grade 4 hematologic toxicity (e.g., neutropenia, thrombocytopenia, anemia). 7. CTCAE Grade 3 or higher non-hematologic organ toxicity, with the following
Immune response to mRNA vaccine
The proportion of activated T cells and IFN-γ content in the peripheral blood, and the T cell receptor (TCR) targeting each mutation were measured after mRNA vaccine treatment.
Response rate to mRNA vaccine
The rates of OS and PFS assessed every 2 months until the end of the study. According to RECIST 1.1 criteria, the patients were divided into complete response (CR), partial response (PR), no change (SD: neither disease progression nor partial response compared with the sum of the minimum long diameters recorded since the beginning of treatment) and progressive disease (PD).
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