A Phase I Clinical Trial of a mRNA Vaccine for Recurrent or Progressive High-grade Glioma

Inclusion criteria

• 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).
• Life expectancy ≥3 months.
• Karnofsky Performance Status (KPS) ≥50. For subjects with spinal cord lesions, functional deficits due to paralysis will not be considered in the KPS assessment.
• Absence of significant bone marrow, cardiac, pulmonary, or renal dysfunction, defined as:

• Hematologic (without transfusion or hematopoietic growth factor support within 14 days):

• Absolute Neutrophil Count (ANC) ≥1.5 × 10⁹/L
• Platelet count (PLT) ≥100 × 10⁹/L
• Hemoglobin (HGB) ≥90 g/L
• Hepatic Function:

• Alanine Aminotransferase (ALT) ≤2.5 × Upper Limit of Normal (ULN)
• Aspartate Aminotransferase (AST) ≤2.5 × ULN
• Total Bilirubin (TBIL) ≤1.5 × ULN
• Renal Function:

• Serum creatinine ≤1.5 × ULN OR estimated creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula)
• Coagulation:

• Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN
• International Normalized Ratio (INR) ≤1.5 × ULN
• Other:

• Left Ventricular Ejection Fraction (LVEF) ≥50% without clinically significant pericardial effusion on echocardiogram
• No clinically significant electrocardiogram (ECG) abnormalities
• Baseline oxygen saturation >92% on room air
• Adequate immune function, defined as receiving dexamethasone ≤2 mg/day within the 3 days prior to screening without severe lymphopenia.
• Negative pregnancy test for women of childbearing potential (WOCBP); non-pregnant and non-lactating females; both male and female participants must agree to use highly effective contraception and have no plan for pregnancy within 6 months after study entry.

Exclusion criteria

• 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.
• Positive serology for:

• Human Immunodeficiency Virus (HIV) antibody
• Hepatitis C Virus (HCV) antibody with detectable HCV RNA
• Hepatitis B Surface Antigen (HBsAg) with HBV DNA ≥2000 IU/mL
• Treponema pallidum (TP) antibody with a positive confirmatory test (e.g., RPR/TPPA)
• Active, uncontrolled infection, active tuberculosis, or active immunosuppressive disease.
• Any concurrent non-malignant illness or psychiatric condition that would preclude safe protocol participation; uncontrolled cardiovascular disease (e.g., coronary artery disease, angina, myocardial infarction, significant arrhythmias).
• Inability or unwillingness to provide informed consent or participate voluntarily.
• Concurrent participation in another interventional clinical trial or participation within 3 months prior to screening.
• Severe infection or signs/symptoms of active infection within 2 weeks prior to the first dose of the investigational product.
• Administration of a live-attenuated vaccine within 4 weeks prior to the first dose.
• History of solid organ or hematopoietic stem cell transplantation.
• Any other condition that, in the opinion of the investigator, would jeopardize the subject's safety or compliance with the study protocol.