Safety and Tolerability of CVGBM in Adults With Newly Diagnosed MGMT-Unmethylated Glioblastoma or Astrocytoma

NCT05938387 | Completed Phase 1 DMC

• 2 other identifiers: CV-GBLM-0012022-501423-25
• Study Type: interventional
• Target: 37
• Locations: 3 countries
• Sites: 13

Brief Summary

This study is an open-label, first-in-human, dose-escalation study of CV09050101 mRNA vaccine (CVGBM) in patients with newly diagnosed "MGMT-unmethylated" Glioblastoma (GBM). Patients with isocitrate dehydrogenase (IDH)-wildtype astrocytoma with a molecular signature of "unmethylated" GBM are also eligible. After surgical resection and completion of radiotherapy for GBM with or without chemotherapy, patients will receive CVGBM i.e. as monotherapy after radiotherapy with or without chemotherapy. The study consists of a dose-escalation part (Part A) which completes enrollment in February 2024 and a dose-expansion part (Part B) which is anticipated to begin enrolling in June/July 2024. Patients will receive a total of 7 administrations of CVGBM on Days 1, 8, 15, 29, 43, 57, and 71. At the discretion of the Investigator in alignment with the Sponsor's medical monitor the vaccinations may continue beyond Day 71 every 6 weeks until one year after the first CVGBM vaccination or upon disease progression or undue toxicity.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (8)

• Incidence of treatment-related adverse events (TRAEs)

  1 year

• Incidence of treatment-emergent adverse events (TEAEs)

  1 year

• Incidence of serious adverse events (SAEs)

  1 year

• Incidence of immune related adverse events (irAEs)

  1 year

• Incidence of injection site reactions (ISRs)

  1 year

• Incidence of clinically significant laboratory abnormalities per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0

  1 year

• Incidence dose-limiting toxicities (DLTs)

  Through the first 2 weeks of treatment

• Severity of DLTs (Unit: Grading via NCI-CTCAE v5.0)

  Through the first 2 weeks of treatment

Secondary Outcomes (4)

• Time to relapse from the day of surgery until the last scheduled visit of the study

  1 year

• Progression-Free Survival (PFS) rate from the day of surgery until the last scheduled visit of the study

  1 year

• Overall survival (OS) rate from the day of surgery until the last scheduled visit of the study

  1 year

• Change in the patients' quality of life measured using a patient-reported-outcome questionnaire

  1 year

Study Arms (6)

Dose escalation: CVGBM Dose Level -1

EXPERIMENTAL

Dose Level -1 represents a dose that may be evaluated if dose level 1 is poorly tolerated. No dose de-escalation below this level is planned for this study. If the dose level -1 is poorly tolerated, the study will be terminated.

Biological: CV09050101 mRNA vaccine (CVGBM) 6 μg

Dose escalation: CVGBM Dose Level 1

EXPERIMENTAL

Biological: CV09050101 mRNA vaccine (CVGBM) 12 μg

Dose escalation: CVGBM Dose Level 2

EXPERIMENTAL

Biological: CV09050101 mRNA vaccine (CVGBM) 25 μg

Dose escalation: CVGBM Dose Level 3

EXPERIMENTAL

Biological: CV09050101 mRNA vaccine (CVGBM) 50 μg

Dose escalation: CVGBM Dose Level 4

EXPERIMENTAL

Biological: CV09050101 mRNA vaccine (CVGBM) 100 μg

Dose expansion

EXPERIMENTAL

After completion of the dose-escalation part and safety data review by the DSMB, approximately 20 patients will be enrolled at the selected Recommended Dose for Expansion (RDE) to generate more data on safety, tolerability and immunogenicity.

Biological: CV09050101 mRNA vaccine RDE 100 μg

Interventions

CV09050101 mRNA vaccine (CVGBM) 12 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose escalation: CVGBM Dose Level 1

CV09050101 mRNA vaccine (CVGBM) 25 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose escalation: CVGBM Dose Level 2

CV09050101 mRNA vaccine (CVGBM) 50 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose escalation: CVGBM Dose Level 3

CV09050101 mRNA vaccine (CVGBM) 100 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose escalation: CVGBM Dose Level 4

CV09050101 mRNA vaccine RDE 100 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose expansion

CV09050101 mRNA vaccine (CVGBM) 6 μg BIOLOGICAL

CVGBM will be administered as an IM injection.

Dose escalation: CVGBM Dose Level -1

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, newly diagnosed GBM (CNS WHO Grade 4) and IDH-wildtype astrocytoma with a molecular signature of "unmethylated" GBM.
• Specific HLA genotype.
• Gross total or partial resection (i.e., ≥50% of tumor volume resected).
• Having completed radiotherapy with or without chemotherapy post-surgery at least 2 weeks before study treatment initiation with no signs of disease progression. Patients must have recovered from any radiotherapy or chemotherapy related side effects to ≤ Grade 1 (with the exception of ALC and WBC as per eligibility criteria). Pretreatment (and concomitant treatment) with TTFields therapy for GBM is allowed.
• Age ≥18 years.
• Karnofsky Performance Status (KPS) ≥70%.
• Life expectancy \>6 months.
• Absolute lymphocyte count (ALC) \>0.5 x109/L.
• Each patient must voluntarily sign and date an informed consent form (ICF) approved by an Independent Ethics Committee (IEC), prior to the initiation of any pre-screening, screening or study-specific procedures. Note: Patients will sign a separate ICF to allow pre-screening/HLA genotyping.
• Female patients who are post-menopausal (no menses for at least 12 months before the Screening Visit), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
• Females of childbearing potential must:
• Have a negative serum pregnancy test with a sensitivity of at least 25 mIU/mL within 10 to 14 days, and within 24 hours prior to starting the study treatment a negative urine pregnancy test.
• Agree to ongoing pregnancy testing during the study.
• Use effective contraception at least 28 days before starting study treatment through to 30 days after the last dose of study treatment. Effective methods of birth control include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

You may not qualify if:

• Hemoglobin \<10 g/dL (6.2 mmol/L)
• White blood cell (WBC) count decrease (\<2.5 x109/L)
• Absolute neutrophil count (ANC) decrease \<1.5 x109/L
• Platelet count decrease \<75 x109/L
• Bilirubin \>1.5 x upper limit of normal (ULN according to the performing lab's reference range), except for patients with Gilbert's syndrome
• Alanine aminotransferase (ALT) \>3 x ULN
• Aspartate aminotransferase (AST) \>3 x ULN
• Gamma glutamyltransferase (GGT) \>2.5 x ULN
• Serum creatinine increased \>1.5 x ULN
• Tumor biopsy only without gross total or partial resection (i.e., ≥50% of tumor volume resected).
• Any prior therapy for GBM (except surgery, radiotherapy with or without chemotherapy (e.g., temozolomide \[TMZ\]), TTFields, and steroids) including immunotherapy.
• Patient on stable or decreasing steroid levels exceeding 10 mg/day prednisone (or equivalent doses of other steroids) during the last 3 days prior to enrollment. Expectation that the patient will need steroid doses \>10 mg/day prednisone or equivalent during the next 3 months. Note: Steroid treatment during the study will be allowed for treatment of cerebral edema or other life-threatening conditions.
• Active human immunodeficiency virus (HIV) infection (ie, CD4 count below the normal range) or active Hepatitis B or C infection (i.e., detectable levels of Hepatitis B DNA or Hepatitis C RNA), or active infections requiring oral or intravenous antibiotics or that can cause a severe disease.
• Clinically relevant autoimmune diseases that could impact the assessment of vaccine safety and efficacy (with the exception of clinically stable thyroid diseases under medication and vitiligo).
• Immunosuppression, not related to prior treatment for malignancy. Any medical condition that requires chronic systemic immunosuppressive therapy including chronic corticosteroids (except physiologic maintenance/replacement doses), methotrexate, tacrolimus or any other immunosuppressive agents within 28 days of treatment start, including, but not limited, to organ transplant-related immunosuppression.

Sponsors & Collaborators

• CureVac: lead

Study Sites (13)

Universitair Ziekenhuis Brussel - PPDS

Brussels, Belgium

Location

CHU de Liège

Liège, Belgium

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Location

University Clinic Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, Germany

Location

University Clinic Regensburg

Regensburg, Bavaria, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, Germany

Location

University Hospital Essen

Essen, North Rhine-Westphalia, Germany

Location

Universitatsklinikum Leipzig

Leipzig, Saxony, Germany

Location

Neurosurgical Clinic at the LMU Munich

München, Germany

Location

Erasmusmc Cancer institute

Rotterdam, South Holland, Netherlands

Location

Related Publications (1)

• Lutz J, Feist RK, Sonntag T, Peguero-Sanchez E, Wolter K, Bick R, Bauer J, Walz JS, Heidenreich R. Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma. Cancer Immunol Immunother. 2025 Oct 6;74(11):329. doi: 10.1007/s00262-025-04178-x.

  PMID: 41051649 DERIVED

MeSH Terms

Conditions

Glioblastoma

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

Study Officials

• Clinical Trial Information

  CureVac SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: July 10, 2023
• Study Start: June 1, 2023
• Primary Completion: February 2, 2026
• Study Completion: February 2, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); DE (10); NL (1)