Evaluation of UCPVax Vaccine +/- Pembrolizumab Combined With Standard Treatment as Adjuvant Therapy in Patients With Unmethylated MGMT Glioblastoma

Exclusion Criteria

• •Patients will not be eligible for this study for any of the following reasons:
• •1. IDH1 or IDH2 mutated tumor
• •2. Presence of extracranial metastasis
• •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.
• •Non-eligible to treatment by UCPVax:
• •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
• •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
• •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))
• •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
• •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
• •Non-eligible to a clinical trial:
• •26. Diagnosis of another malignant tumor within 2 years before randomization except treating resected basocellular carcinoma and carcinoma in situ such as breast cancer, endometrial or cervical carcinoma that have undergone curative therapy.
• •27. Current or treatment with another investigational drug within the previous 4 weeks.
• •28. Breast-feeding or pregnant women, no effective contraception if risk of conception exists (up to 4 months after end of chemotherapy)