New adjuvant vaccine in glioblastoma, a Phase 1/2a study (NAVIG-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Nov 2024 → ongoing

Decision date (initial)

2024-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Altevax SAS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

In phase 1: to assess the maximum tolerated dose (MTD) and select the recommended Phase 2a dose.
In phase 2a : to assess anti-TERT specific T cell responses at 2 months at the selected dose level.

Secondary objectives 6

1. To assess anti-PTPRZ1 and anti-TERT immune T cell responses triggered by the vaccination protocol (Phase 1)
2. To assess Safety
3. To assess Progression free survival (RANO 2.0 criteria)
4. To assess Overall survival
5. To assess Quality of life by EORTC QLQ30 and BN20 questionnaires
6. 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

Conditions and MedDRA coding

glioblastoma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

Yes

IPD plan description

All of the individual participant data collected during the trial, subject to compliance to regulations, will be available. Document (Study protocol, statistical analysis plan, informed consent form, clinical study report, analytic code) will be also available. Data will be available immediately following publication ending 2 years after publication, with investigators whose proposed use of the data has been approved by the PI and / or the review commitee if relevant. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age between 18 and 75 years old
2. Free, informed and written consent signed
3. Histologically confirmed glioblastoma
4. 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.
5. Karnofsky Performance Status ≥ 60%
6. Phase 1 only : Patients must be human leukocyte antigen (HLA)-A2 positive
7. Phase 1 only : PTPRZ1 expression in the tumor
8. Available tumor tissue for post hoc (retrospective) assessment of TERT promoter mutations and MGMT promoter methylation status
9. Life expectancy ≥ 3 months
10. Adequate organ function laboratory values within 15 days before initiation of treatment (see table in section 6.1)
11. 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.
12. Patient affiliated to the social security scheme

Exclusion criteria 17

1. Known extracranial metastatic or leptomeningeal disease
2. Grade 4 astrocytoma IDH mutant
3. Steroid requirement >10 mg prednisone daily (or equivalent) at time of inclusion
4. Patients with prior malignancy active within the last 3 years
5. Patients receiving immunomodulatory or immunosuppressive therapy
6. Carmustine wafers (GliadelR) implantation during surgery
7. Phase 1 only: patient eligible and willing to be treated with Optune (TTF fields)
8. History of autoimmune disease (lupus, rheumatoid arthritis, inflammatory bowel disease...)
9. Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
10. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
11. 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
12. Breast-feeding or pregnant women
13. Contra-indications to MRI
14. Contra-indications to investigational medicinal product and/or to auxiliary medicinal products
15. 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
16. Patient unable to follow the procedures and constraints of the protocol
17. Patient under legal protection (protection of the court, or in curatorship or guardianship)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1 : Safety. Safety AEs will be evaluated and graded according to CTCAE v5.0 a) clinically at D0, W2, W4, W6, M2, M3, M4, M5, M7, M9, M11 and M12 ; b) with blood samples at D0, W2, W4, W6, M2, M3, M5, M7, M9, M11 and M12 ; c) with cerebral MRI at baseline, M2, M3 and every 2 months thereafter. Phase 2a : immune efficacy: anti-TERT specific T cell responses in peripheral blood using IFN-gamma ELISPOT at 2 months post first immunizations.

Secondary endpoints 7

1. Evolution over time of anti-PTPRZ1 and anti-TERT immune T cell responses triggered by the vaccination protocol in peripheral blood using IFN-gamma ELISPOT before and during treatment (W2 for phase 1 only, W4, M2, M3, M5, M7, M9 and M12)
2. Short and long-time safety, assessed clinically at D0, W2, W4, W6, M2, M3, M4, M5, M7, M9, M11 and M12 and with blood samples at D0, W2, W4, W6, M2, M3, M5, M7, M9, M11 and M12
3. Progression free survival with cerebral MRI at baseline, M2, M3 and every 2 months thereafter
4. Overall survival
5. Quality of life by EORTC QLQ30 and BN20 questionnaires at baseline and at 5 months
6. Cardiac safety in a cohort of 8 patients enrolled in the Phase 2a study assessed at D0 (pre injection and D0 + 3 hours), day 7, W2 and M2 and with blood samples at D0, W2 and M2
7. Circulating anti-melanin antibodies at baseline and M2 in a cohort of 8 patients enrolled in the Phase 2a

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Antoine CARPENTIER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Antoine CARPENTIER

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications