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

Prospective multicentre Phase I- IIa, non-comparative, non-randomised study with escalating doses for the Phase 1 part.

Therapeutic cancer vaccines consisting of 1 or 2 antigenic peptidic formulations combined with an immune adjuvant:

• A52-Mel: a TERT peptidic epitope adsorbed on synthetic melanin
• A49-Mel: a PTPRZ1 peptidic epitope adsorbed on synthetic melanin (Phase 1 only)
• Litenimod, a TLR9 agonist, as an adjuvant

Phase 1: Patients will receive subcutaneous injections in the shoulders of both A49 and A52 at one of 3 pre-specified dose levels of peptides (50-100-250µg) + 1mg of Litenimod (fixed dose).

Phase 2a: Patients will receive subcutaneous injections in the shoulder of A52 only at the dose selected in the phase 1 part + 1mg of Litenimod

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) with concomitant temozolomide, before the beginning of the 6 additional monthly cycles of temozolomide. Radiation therapy must have been completed 28 to 45 days prior to the first 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 promoter mutations and MGMT promoter methylation status
• Life expectancy ≥ 3 months
• Adequate organ function laboratory values within 15 days before initiation of treatment (see table in section 6.1)
• Women or Male of childbearing potential (WOCBP) must use contraceptive methods during and for 180 days after the last dose of temozolomide or up to 120 days after the last dose of vaccine, whichever is longer (see section 6.3). No sperm donation during 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 bowel disease...)
• Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
• Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study.
• 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
• Breast-feeding or pregnant women.
• Contra-indications to IRM
• Contra-indications to investigational medicinal product and/or to auxiliary medicinal products
• Participation to another interventional clinical trial, clinical investigation or another interventional study or being in the exclusion period at the end of a previous study
• Patient unable to follow the procedures and constraints of the protocol
• Patient under legal protection (protection of the court, or in curatorship or guardianship).