New Adjuvant Vaccine in Glioblastoma, a Phase 1/2a Study (NAVIG-1)
This phase I/II trial evaluates the safety and the immunological efficacy of a cancer vaccine against 2 glioma-associated antigens in newly-diagnosed glioblastomas. The objectives of this study are as follows: Primary objective * phase 1: * to assess the maximum tolerated dose (MTD) and select the recommend Phase 2a dose * phase 2a: * to assess anti- TERT specific T cell responses at 2 months at the selected dose level Secondary objectives: * To assess Short and long-time immunological safety * To assess Evolution of anti-PTPRZ1 and anti-TERT immune T cell responses over time * To assess Progression free survival (RANO 2.0 criteria) * To assess Overall survival * To assess Quality of life by EORTC QLQ30 and BN20 questionnaires as well as objective of ancillary study: to determine the mechanism of action of potential tumour escape in GBM (T-cell lymphocyte phenotype; antigen expression and checkpoint inhibitors on tumour cells at relapse, if available), analysis of circulating antibodies against TERT epitope and/or melanin, and identification of predictive biomarkers of response. Ultimately, this trial together will lead to the implementation of future phase III trial in GBM. All patients enrolled in the study will receive standard treatment consisting of surgical resection of the tumor followed by radio-chemotherapy. Immunotherapy will begin 4 weeks after the completion of radiotherapy.
• 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