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

NCT07306299 | Recruiting Phase 1 DMC

• 1 other identifier: 2025LSYD1864
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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.

Conditions

Glioma, High Grade

Keywords

Glioma; mRNA vaccine; Mutation

Outcome Measures

Primary Outcomes (1)

• 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

  2-3 years

Secondary Outcomes (1)

• Immune response to mRNA vaccine

  1-5 years

Other Outcomes (1)

• Response rate to mRNA vaccine

  2-5 years

Study Arms (1)

mRNA vaccine treatment group

EXPERIMENTAL

Participants in this arm receive the glioma-related multi-trageted mRNA vaccine.

Biological: Glioma-related multi-target mRNA vaccines

Interventions

Glioma-related multi-target mRNA vaccines BIOLOGICAL

Multi-targeted mRNA vaccines encoding the following GBM-associated mutations: H3.3K27M, H3.1K27M, H3.3G34R, BRAFV600E, PIK3CAH1047R, IDH1R132H, EGFRvIII

Also known as: mV002

mRNA vaccine treatment group

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Room 521, Building 12, Jiefang Road Campus, The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Yongjian Zhu, M.D., Ph.D

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingyu Wang, M.D., Ph.D

CONTACT

+86 15990016248; wangjingyu1@zju.edu.cn

Qiangwei Wang, M.D., Ph.D

CONTACT

+86 17815700579

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: December 14, 2025
• First Posted: December 29, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2031
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: starting 6 months after publication
• Access Criteria: All

Locations

CN (1)