New Adjuvant Vaccine in Glioblastoma, a Phase 1/2a Study

Inclusion Criteria:

• age between 18 and 75 years old

• free, informed and written consent signed

• Histologically confirmed glioblastoma

• Patients previously treated with concurrent radiotherapy (at least 45 Gy) withconcomitant temozolomide, before the beginning of the 6 additional monthly cycles oftemozolomide. Radiation therapy must have been completed 28 to 45 days prior to thefirst study treatment

• Karnofsky Performance Status ≥ 60%

• Phase 1 only: Patients must be human leukocyte antigen (HLA)-A2 positive.

• Phase 1 only: PTPRZ1 expression in the tumor

• Available tumor tissue for post hoc (retrospective) assessment of TERT promotermutations and MGMT promoter methylation status

• Life expectancy ≥ 3 months

• Adequate organ function laboratory values within 15 days before initiation oftreatment (see table in section 6.1)

• Women or Male of childbearing potential (WOCBP) must use contraceptive methodsduring and for 180 days after the last dose of temozolomide or up to 120 days afterthe last dose of vaccine, whichever is longer (see section 6.3). No sperm donationduring the study and until 7 months after the end of the treatment period.

• Patient affiliated to the social security scheme

Exclusion Criteria:

• Known extracranial metastatic or leptomeningeal disease

• Grade 4 astrocytoma IDH mutant

• Steroid requirement >10 mg prednisone daily (or equivalent) at time of inclusion

• Patients with prior malignancy active within the last 3 years

• Patients receiving immunomodulatory or immunosuppressive therapy

• Carmustine wafers (GliadelR) implantation during surgery

• Phase 1 only: patient eligible and willing to be treated with Optune (TTF fields)

• History of autoimmune disease (lupus, rheumatoid arthritis, inflammatory boweldisease...)

• Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists

• Patient with any medical or psychiatric condition or disease, which would make thepatient inappropriate for entry into this study.

• Uncontrolled active systemic fungal, bacterial, viral, or other infection within theprevious 4 weeks or requirement for intravenous (IV) antibiotics within the last twoweeks

• Breast-feeding or pregnant women.

• Contra-indications to IRM

• Contra-indications to investigational medicinal product and/or to auxiliarymedicinal products

• Participation to another interventional clinical trial, clinical investigation oranother interventional study or being in the exclusion period at the end of aprevious study

• Patient unable to follow the procedures and constraints of the protocol

• Patient under legal protection (protection of the court, or in curatorship orguardianship).