Evaluation of UCPVax and Pembrolizumab with Standard Therapy in Adjuvant Treatment of Unmethylated MGMT Glioblastoma
- Trial ID
- 2024-514399-42-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the 18-month overall survival following randomization in patients diagnosed with unmethylated glioblastoma receiving UCPVax with or without pembrolizumab in combination with standard treatment consisting of temozolomide and potentially tumor treating fields. The secondary objectives include:
- Assessment of 18-month overall survival in the control arm receiving standard treatment.
- Evaluation of overall survival across all study arms.
- Determination of progression-free survival since randomization and at 6 months across all study arms.
- Assessment of the safety profile in all study arms.
- Evaluation of immunogenicity for the combination therapy in the experimental arms.
- Measurement of health-related quality of life across all study arms.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with glioblastoma. Eligible participants must be aged 18 years or older and have a confirmed histological diagnosis of non-mutated IDH primary glioblastoma. Further requirements include an unmethylated MGMT promoter status and the completion of concomitant radiotherapy plus temozolomide. Participants must demonstrate a Karnofsky Performance Status of at least 70% and have a life expectancy of at least 3 months. Inclusion requires stable corticosteroid dosing and adequate organ function. Female participants of childbearing potential must utilize highly effective contraception or meet specific criteria for being postmenopausal.
Plans and Procedures
This Phase II clinical trial is designed to evaluate the efficacy of the UCPVax vaccine, both with and without the addition of pembrolizumab, when administered as adjuvant therapy alongside standard treatment for patients diagnosed with glioblastoma presenting with an unmethylated MGMT promoter. The standard treatment regimen includes temozolomide. The primary efficacy endpoint is the overall survival rate measured at 18 months following randomization. Secondary objectives include the assessment of progression-free survival according to RANO 2.0 criteria, immunogenicity via IFN-γ ELISpot, and health-related quality of life using the EORTC-QLQC30 and BN20 modules. The study involves a screening phase to confirm histological diagnosis and eligibility, followed by the treatment period and subsequent follow-up evaluations. Participant involvement is monitored through routine adverse events assessment and laboratory evaluations. The trial is estimated to conclude by April 2029.
Treatment
The experimental treatment UCPVax is an emulsion for injection containing UCP4. The administered dosage is 0.5 mg provided in a solution for injection.
Pembrolizumab is administered as a solution for infusion at a dosage of 400 mg.
Standard treatment consists of temozolomide, which is administered for oral use at a dose of 150 mg/m².
Efficacy
The primary efficacy endpoint is the rate of patients alive at 18 months post-randomization in each experimental arm. Secondary efficacy assessments include overall survival, defined as the time interval from randomization to death from any cause, with alive patients censored at the last known date of survival. Progression-free survival will be evaluated according to RANO 2.0 criteria, measured as the time from randomization to the first documented disease progression or death from any cause.
Further evaluations involve the following parameters:
- Immunogenicity, assessed via ex vivo IFN-γ ELISpot in peripheral blood.
- Health-related quality of life, measured using the EORTC-QLQC30 questionnaire and BN20 module at randomization and at 6 months.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 1 - Male or female, age ≥ 18 with informed consent signed
- 2 - Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy).
- 3- Tumor with unmethylated MGMT promoter status
- 4- Patients having completed the concomitant phase of radiotherapy + temozolomide regimen, and eligible for the 6 monthly cycles of maintenance temozolomide
- 5- Karnofsky Perfomance status (KPS) ≥ 70%
- 6- Life expectancy ≥ 3 months
- 7- If patient is treated by corticosteroïds (CS), patient must be on stable CS dose for 15 days and total daily dose ≤ 10 mg prednisone, or equivalent
- 8- Adequate organ function laboratory values:
- 9- Females must be using highly effective contraceptive measures (see Section V-5-1), and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening : o Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. o Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution. o Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- 10- Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.
- 11- Patient affiliated to or beneficiary of French social security system
- 12- Ability to comply with the study protocol, in the Investigator’s judgment.
- 13- Signed and dates informed consent
Exclusion Criteria
- 1- IDH1 or IDH2 mutated tumor
- 10- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
- 11- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- 12- History of tuberculosis infection
- 13- History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- 14- Active auto-immune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroïds or immunosuppressors). Replacement therapy (e.g. thyroxine, insulin) is allowed.
- 15- Active or history of auto-immune disease or immune deficiency (see Appendix 7 for more details)
- 16- History of solid organ transplant nor allogenic hematopoietic stem cell transplantation
- 17- Hypersensitivity to the active substance temozolomide or to any of the excipients listed (anhydrous lactose, colloidal anhydrous silica, sodium carboxymethyl starch type A, tartaric acid, stearic acid),
- 18- Hypersensitivity to dacarbazine (DTIC )
- 19- Hypersensitivity to the active substance pembrolizumab or to any of the excipients listed (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433))
- 2- Presence of extracranial metastasis
- 20- Hypersensitivity to the active substance Montanide
- 21- Uncontrolled active systemic fungal, bacterial, viral, or other infection within the previous 4 weeks or requirement for intravenous (IV) antibiotics within the last two weeks
- 22- Inadequate hematology and organ functions; known cardiac failure or unstable coronaropathy, respiratory failure or another life threatening condition.
- 23- Patient with unresolved non-hematologic toxicities > Grade 1 (or > Grade 2 if deemed acceptable by the investigator and not considered a safety risk )
- 24- Major surgery within 1 month prior randomization or planned during the study
- 3- Leptomeningeal disease on MRI
- 4- Contrast enhancement ≥4 cm (largest diameter on axial T1 sequences) on inclusion MRI
- 5- Previous treatment with Carmustine impregnated wafers (GliadelR)
- 6- Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
- 7- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study.
- 8- Prior therapy with an anti-PD-1, anti-PD-L1, or with an agent directed to another immune checkpoint (e.g. CTLA-4, TIGIT, Lag3…).
- 9- Immunosuppressive treatment including CS > 10 mg prednisone or equivalent within the previous 2 weeks
- 25- Vaccination with alive attenuated vaccine within 4 weeks prior the first dosing. Patient must agree not to receive live attenuated vaccine including influenza vaccine during the treatment and within 6 months following the last dose of pembrolizumab
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Oct 2025 | 98 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PEMBROLIZUMAB | Test | — | SOLUTION FOR INFUSION | 400 | 14 | SUB167136 |
UCPVax 1mg/2ml | Test | EMULSION FOR INJECTION | SOLUTION FOR INJECTION | 0.5 | 14 | PRD5563328 |
TEMOZOLOMIDE | Test | — | ORAL USE | 150 | 6 | SUB10889MIG |