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

Korábbi kezelés

• Previous treatment with Carmustine impregnated wafers (GliadelR)
• Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
• 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…).
• Immunosuppressive treatment including CS > 10 mg prednisone or equivalent within the previous 2 weeks
• 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.
• 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
• Major surgery within 1 month prior randomization or planned during the study
• 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:
• Current or treatment with another investigational drug within the previous 4 weeks.
• Breast-feeding or pregnant women, no effective contraception if risk of conception exists (up to 4 months after end of chemotherapy)

Más betegség

• Cancer specific exclusion criteria:
• Leptomeningeal disease on MRI
• 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:
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• History of tuberculosis infection
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• 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.
• Active or history of auto-immune disease or immune deficiency
• History of solid organ transplant nor allogenic hematopoietic stem cell transplantation
• Hypersensitivity to dacarbazine (DTIC)
• Hypersensitivity to the active substance pembrolizumab or to any of the excipients listed (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433))
• Hypersensitivity to the active substance Montanide
• Inadequate hematology and organ functions; known cardiac failure or unstable coronaropathy, respiratory failure or another life threatening condition.
• 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.

Laborértékek

• 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),

Egyéb

• Patients will not be eligible for this study for any of the following reasons:
• IDH1 or IDH2 mutated tumor
• Presence of extracranial metastasis
• Contrast enhancement ≥4 cm (largest diameter on axial T1 sequences) on inclusion MRI
• Patient with unresolved non-hematologic toxicities > Grade 1 (or > Grade 2 if deemed acceptable by the investigator and not considered a safety risk)

• Male or female, age ≥ 18 with informed consent signed
• Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy).
• Tumor with unmethylated MGMT promoter status
• Patients having completed the concomitant phase of radiotherapy + temozolomide regimen (standard radiotherapy with 60 Gy in 30 fractions or hypofractionated radiotherapy with 40 Gy in 15 fractions), and eligible for the 6 monthly cycles of maintenance temozolomide
• Karnofsky Perfomance status (KPS) ≥ 70%
• Life expectancy ≥ 3 months
• 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
• Adequate organ function laboratory values
• Females must be using highly effective contraceptive measures, 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 :
  • Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
  • 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.
  • Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but tubal ligation.
  • Female with childbearing potential must use effective contraception during study treatment and after the end of treatment based on the last study drug administrated: 6 months after the last dose of Temozolomide; 4 months after the last dose of pembrolizumab and 1 month after the last injection of UCPVax.
• Male patients with a female partner of childbearing potential should be willing to use barrier contraception and to refrain from donating sperm during the study and and post-treatment based on the last study drug administrated: 3 months after the last dose of temozolomide; 4 months after the last pembrolizumab dose; 1 month after the last UCPVax injection.
• Patient affiliated to or beneficiary of French social security system
• Ability to comply with the study protocol, in the Investigator's judgment.
• Signed and dates informed consent