PEMBROLIZUMAB for Glioblastoma|Glioblastoma (MGMT promoter unmethylated)

Inclusion criteria

• {"criterion_text":"- 1 - Male or female, age ≥ 18 with informed consent signed"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 11- Patient affiliated to or beneficiary of French social security system"}
• {"criterion_text":"- 12- Ability to comply with the study protocol, in the Investigator’s judgment."}
• {"criterion_text":"- 13- Signed and dates informed consent"}
• {"criterion_text":"- 2 - Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy)."}
• {"criterion_text":"- 3- Tumor with unmethylated MGMT promoter status"}
• {"criterion_text":"- 4- Patients having completed the concomitant phase of radiotherapy + temozolomide regimen, and eligible for the 6 monthly cycles of maintenance temozolomide"}
• {"criterion_text":"- 5- Karnofsky Perfomance status (KPS) ≥ 70%"}
• {"criterion_text":"- 6- Life expectancy ≥ 3 months"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 8- Adequate organ function laboratory values:"}
• {"criterion_text":"- 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\tPost-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. o\tWomen 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\tWomen with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation."}

Exclusion criteria

• {"criterion_text":"- 1-\tIDH1 or IDH2 mutated tumor"}
• {"criterion_text":"- 18-\tHypersensitivity to dacarbazine (DTIC )"}
• {"criterion_text":"- 19-\tHypersensitivity to the active substance pembrolizumab or to any of the excipients listed (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433))"}
• {"criterion_text":"- 2-\tPresence of extracranial metastasis"}
• {"criterion_text":"- 20-\tHypersensitivity to the active substance Montanide"}
• {"criterion_text":"- 21-\tUncontrolled active systemic fungal, bacterial, viral, or other infection within the previous 4 weeks or requirement for intravenous (IV) antibiotics within the last two weeks"}
• {"criterion_text":"- 22-\tInadequate hematology and organ functions; known cardiac failure or unstable coronaropathy, respiratory failure or another life threatening condition."}
• {"criterion_text":"- 23-\tPatient with unresolved non-hematologic toxicities > Grade 1 (or > Grade 2 if deemed acceptable by the investigator and not considered a safety risk )"}
• {"criterion_text":"- 24-\tMajor surgery within 1 month prior randomization or planned during the study"}
• {"criterion_text":"- 3-\tLeptomeningeal disease on MRI"}
• {"criterion_text":"- 4-\tContrast enhancement ≥4 cm (largest diameter on axial T1 sequences) on inclusion MRI"}
• {"criterion_text":"- 10-\tConcurrent 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."}
• {"criterion_text":"- 5-\tPrevious treatment with Carmustine impregnated wafers (GliadelR)"}
• {"criterion_text":"- 6-\tPrevious treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists"}
• {"criterion_text":"- 7-\tPatient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study."}
• {"criterion_text":"- 8-\tPrior therapy with an anti-PD-1, anti-PD-L1, or with an agent directed to another immune checkpoint (e.g. CTLA-4, TIGIT, Lag3…)."}
• {"criterion_text":"- 9-\tImmunosuppressive treatment including CS > 10 mg prednisone or equivalent within the previous 2 weeks"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 11-\tHas a known history of Human Immunodeficiency Virus (HIV) infection."}
• {"criterion_text":"- 12-\tHistory of tuberculosis infection"}
• {"criterion_text":"- 13-\tHistory of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease."}
• {"criterion_text":"- 14-\tActive 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."}
• {"criterion_text":"- 15-\tActive or history of auto-immune disease or immune deficiency (see Appendix 7 for more details)"}
• {"criterion_text":"- 16-\tHistory of solid organ transplant nor allogenic hematopoietic stem cell transplantation"}
• {"criterion_text":"- 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),"}

Primary endpoints

• {"endpoint_text":"- In each experimental arms, the primary endpoint for the efficacy is the rate of patients alive at 18 months post randomization","definition_or_measurement_approach":"Proportion (rate) of patients alive at 18 months after randomization (Overall Survival status at 18 months post-randomization)."}

Secondary endpoints

• {"endpoint_text":"- The rate of patients alive at 18 months post randomization","definition_or_measurement_approach":"Proportion (rate) of patients alive at 18 months post-randomization (same measure as primary in control arm)."}
• {"endpoint_text":"- Overall survival (OS) defined as the time interval from randomization to the date of death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period","definition_or_measurement_approach":"Time-to-event measure: interval from randomization to death from any cause; censoring at last known alive date."}
• {"endpoint_text":"- Progression free survival (PFS) according to RANO 2.0 criteria: defined as the time interval from the date of randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation showing no progression during study treatment follow-up.","definition_or_measurement_approach":"Time-to-event per RANO 2.0 criteria: from randomization to first documented progression or death; censoring at last radiological evaluation without progression."}
• {"endpoint_text":"- Adverse events and routine lab abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0, see Appendix 2), timing, seriousness and relationship to study treatments at each visit.","definition_or_measurement_approach":"Safety reporting aggregated by type, frequency and severity graded by NCI CTCAE v5.0; assessment of seriousness and relationship to study treatments at each visit."}
• {"endpoint_text":"- Immunogenecity will be assess by ex vivo IFN-γ ELISpot in peripheral blood (Adotevi JCO 2023).","definition_or_measurement_approach":"Immunogenicity measured by ex vivo IFN-γ ELISpot on peripheral blood samples."}
• {"endpoint_text":"- Health related Quality of life will be evaluated with EORTC-QLQC30 questionnaire and BN20 module at randomization and at 6 months.","definition_or_measurement_approach":"Patient-reported outcomes assessed using EORTC QLQ-C30 and BN20 module at baseline (randomization) and at 6 months."}

France

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

21

Number Of Sites

4

Number Of Participants

98

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France