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

Phase 1

Recruiting

Brief Summary: 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. 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.

Detailed Description: This therapeutic vaccine targeting 2 identified glioma-associated antigens (TERT and PTPRZ1) is based on a new formulation that contains synthetic melanin and a TLR9 agonist, which is caable to induce strong cellular immune responses.

One month after glioblastoma patients have completed the initial phase of treatment with concurrent radiochemotherapy, patients will be immunized during the adjuvant phase of monthly temozolomide. Immunizations will follow the standard schedule of a priming phase (D0, W2, W4, and W6) followed by a boost phase with one immunization every 2 months for a total of 12 months.

Phase 1: subcutaneous injections at one of 3 pre-specified dose levels of peptides Phase 2a: subcutaneous injections at the dose selected in the phase 1 part. Safety will be evaluated clinically and with blood samples at each treatment visit. Efficacy will be assessed with anti-PTPRZ1 and anti-TERT specific T cell responses in peripheral blood, and with cerebral MRI every other months

Recruitment & Eligibility

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%
Patients must be human leukocyte antigen (HLA)-A2 positive.
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).

Arm && Interventions

Group	Intervention	Description
A52-Mel/A49-Mel/Li28	immunization	One month after completion of concurrent radiochemotherapy, patients will be immunized during the adjuvant phase of monthly temozolomide with subcutaneous injections of the vaccine formulation (D0, W2, W4, W6, and then every 2 months until progression) consisting of 2 tumor antigens (TERT and PTPRZ1) adjuvanted with synthetic melanin and a TLR9 agonist (CpG-ODN).

Primary Outcome Measures

Name	Time	Method
safety/efficacy	2 months	- phase 2a : to assess anti-PTPRZ1/ TERT specific T cell responses

Secondary Outcome Measures

Name	Time	Method
Progression free survival	12 months	Tumor response will be assessed using RANO 2.0 criteria
the evaluation of quality of life	5 months	EORTC-QLQC30 questionnaire and BN20 module will be completed by each patient (Not all= 1; A little=2; Quite a bit= 3 ; Very Much=4)
Overall survival	12 months	The time interval from the start of treatment to the date of death from any cause.

Locations (1): Department of Neurology, Hopital Saint louis (APHP)
🇫🇷
Paris, France