New Adjuvant Vaccine in Glioblastoma, a Phase 1/2a Study (NAVIG-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose (MTD) for Phase 1
研究概览
简要总结
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
- To evaluate cardiac safety and monitor for the potential development of anti-melanin antibodies in a cohort of 8 patients enrolled in the Phase 2a study
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
A52-Mel; A49-Mel (for Phase1 only) and Litenimod, as an adjuvant
In Phase 1, A52-Mel and A49-Mel will be mixed just prior to the injection. Litenimod will be injected at the same site just after the injection.
In phase 2a, A52-Mel was initially administered as a standalone injection, followed by Litenimod at the same injection site. Then, an optimized procedure allows the injection of A52-Mel and Litenimod simultaneously, the two components being mixed extemporaneously prior to the injection.
干预措施: immunization (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) for Phase 1
时间窗: 2 months
the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicity (DLT)
safety/efficacy
时间窗: 2 months
\- phase 2a : to assess anti-PTPRZ1/ TERT specific T cell responses
anti-PTPRZ1 specific T cell responses (safety/efficay) for Phase 1
时间窗: 12 months
anti-PTPRZ1 specific T cell responses by using IFN-gamma ELISPOT
anti-TERT specific T cell responses (safety/efficay) for Phase 1
时间窗: 12 months
anti-TERT specific T cell responses by using IFN-gamma ELISPOT
anti-TERT specific T cell responses (safety/efficay) for Phase 2
时间窗: 2 months
anti-TERT specific T cell responses by using IFN-gamma ELISPOT
次要结局
- Progression free survival(12 months)
- the evaluation of quality of life(5 months)
- Overall survival(12 months)
- Circulating anti-melanin antibodies(At M2)
- Cardiac safety(At month 2)
- Evolution of anti-PTPRZ1 specific T cell responses(over time)
- Evolution of anti-TERT specific T cell responses(over time)