Glioblastoma
Conditions
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.
Interventions
BIOLOGICALCV09050101 mRNA vaccine (CVGBM) 12 μg
CVGBM will be administered as an IM injection.
BIOLOGICALCV09050101 mRNA vaccine (CVGBM) 25 μg
CVGBM will be administered as an IM injection.
BIOLOGICALCV09050101 mRNA vaccine (CVGBM) 50 μg
CVGBM will be administered as an IM injection.
BIOLOGICALCV09050101 mRNA vaccine (CVGBM) 100 μg
CVGBM will be administered as an IM injection.
BIOLOGICALCV09050101 mRNA vaccine RDE 100 μg
CVGBM will be administered as an IM injection.
BIOLOGICALCV09050101 mRNA vaccine (CVGBM) 6 μg
CVGBM will be administered as an IM injection.
Sponsors
CureVac
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed, newly diagnosed GBM (CNS WHO Grade 4) and IDH-wildtype astrocytoma with a molecular signature of "unmethylated" GBM. 2. Specific HLA genotype. 3. Gross total or partial resection (i.e., ≥50% of tumor volume resected). 4. 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. 5. Age ≥18 years. 6. Karnofsky Performance Status (KPS) ≥70%. 7. Life expectancy \>6 months. 8. Absolute lymphocyte count (ALC) \>0.5 x109/L. 9. 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. 10. 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: 1. 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. 2. Agree to ongoing pregnancy testing during the study. 3. 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: * oral * intravaginal * transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation: * oral * injectable * implantable * intrauterine device * intrauterine hormone-releasing system * bilateral tubal occlusion * vasectomised partner + barrier method * sexual abstinence: Either agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal (coitus interruptus), spermicides only and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. 11. Male patients, even if surgically sterilized (i.e., status postvasectomy), must: 1. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal (coitus interruptus), spermicides only and LAM are not acceptable methods of contraception. 2. Agree to practice effective barrier contraception during the entire study treatment period (e.g., condom) and through to 3 months after the last dose of study treatment if their partner is of childbearing potential, even if they have had a successful vasectomy.
Exclusion criteria
1. Abnormal (≥Grade 2 NCI-CTCAE v5.0) laboratory values for hematology, liver and renal function (serum creatinine). The following values apply as
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of injection site reactions (ISRs) | 1 year |
| Incidence of immune related adverse events (irAEs) | 1 year |
| 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 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Belgium, Germany, Netherlands
Contacts
STUDY_DIRECTORClinical Trial Information
CureVac SE
Outcome results
None listed