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

NCT06622434 | Recruiting Phase 1 DMC

• 2 other identifiers: APHP2405122024-514567-26-00
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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. 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.

Conditions

Newly Diagnosed Glioblastoma

Keywords

Cancer vaccine; Glioblastoma; Telomerase; TERT; PTPRZ1; Immunomodulation

Outcome Measures

Primary Outcomes (3)

• anti-PTPRZ1 specific T cell responses (safety/efficay) for Phase 1

  anti-PTPRZ1 specific T cell responses by using IFN-gamma ELISPOT

  12 months

• anti-TERT specific T cell responses (safety/efficay) for Phase 1

  anti-TERT specific T cell responses by using IFN-gamma ELISPOT

  12 months

• anti-TERT specific T cell responses (safety/efficay) for Phase 2

  anti-TERT specific T cell responses by using IFN-gamma ELISPOT

  2 months

Secondary Outcomes (5)

• Overall survival

  12 months

• Progression free survival

  12 months

• the evaluation of quality of life

  5 months

• Evolution of anti-PTPRZ1 specific T cell responses

  over time

• Evolution of anti-TERT specific T cell responses

  over time

Study Arms (1)

A52-Mel; A49-Mel (for Phase1 only) and Litenimod, as an adjuvant

EXPERIMENTAL

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 will be administered, followed by Litenimod at the same injection site.

Biological: immunization

Interventions

immunization BIOLOGICAL

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).

A52-Mel; A49-Mel (for Phase1 only) and Litenimod, as an adjuvant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Known extracranial metastatic or leptomeningeal disease
• Grade 4 astrocytoma IDH mutant
• 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
• Patient unable to follow the procedures and constraints of the protocol
• Patient under legal protection (protection of the court, or in curatorship or guardianship).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (5)

Department of Neurology, University Hospital of Besançon

Besançon, Bourgogne-Franche-Comté, 25030, France

NOT YET RECRUITING

Medical Oncology Department, Eugène Marquis Centre

Rennes, Brittany Region, 35000, France

NOT YET RECRUITING

Department of Neurology, Hopital de la Salpêtrière

Paris, Idf, 75013, France

RECRUITING

Neuro-oncology Department, La Timone Hospital

Marseille, Provence-Alpes-Côte d'Azur Region, 13005, France

NOT YET RECRUITING

Department of Neurology, Hopital Saint louis (APHP)

Paris, 75010, France

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Immunization

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health

Study Officials

• Antoine CARPENTIER, Pr

  APHP- Hôpital Saint Louis

  STUDY CHAIR

Central Study Contacts

Antoine CARPENTIER, Pr

CONTACT

0171207466; antoine.carpentier@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: October 2, 2024
• Study Start: November 8, 2024
• Primary Completion (Estimated): March 8, 2028
• Study Completion (Estimated): March 8, 2028
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

FR (5)