Evaluation of Ucpvax Vaccine +/- Pembrolizumab Combined with Standard Treatment as Adjuvant Therapy in Patients with Unmethylated Glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-11-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the two experimental arms with UCPVax +/- pembrolizumab combined with standard treatment( Temozolomide +/- NovoTTF-200A)

Secondary objectives 7

1. To assess the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the control arm receiving standard treatment: Temozolomide +/- NovoTTF-200A).
2. To assess the Overall Survival (OS) in the three arms.
3. To assess the progression free survival (PFS) since randomization in the the three arms
4. To assess the progression free survival (PFS) at 6 month since randomization in the the three arms.
5. To evaluate overall safety profile in the three arms
6. To assess the immunogenicity of the proposal combination therapy in the two experimental arms.
7. To evaluate health-related quality of life (HrQoL) in the three arms

Conditions and MedDRA coding

Glioblastoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1 - Male or female, age ≥ 18 with informed consent signed
2. 2 - Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy).
3. 3- Tumor with unmethylated MGMT promoter status
4. 4- Patients having completed the concomitant phase of radiotherapy + temozolomide regimen, and eligible for the 6 monthly cycles of maintenance temozolomide
5. 5- Karnofsky Perfomance status (KPS) ≥ 70%
6. 6- Life expectancy ≥ 3 months
7. 7- If patient is treated by corticosteroïds (CS), patient must be on stable CS dose for 15 days and total daily dose ≤ 10 mg prednisone, or equivalent
8. 8- Adequate organ function laboratory values:
9. 9- Females must be using highly effective contraceptive measures (see Section V-5-1), and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening : o Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. o Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution. o Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
10. 10- Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.
11. 11- Patient affiliated to or beneficiary of French social security system
12. 12- Ability to comply with the study protocol, in the Investigator’s judgment.
13. 13- Signed and dates informed consent

Exclusion criteria 25

1. 1- IDH1 or IDH2 mutated tumor
2. 10- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
3. 11- Has a known history of Human Immunodeficiency Virus (HIV) infection.
4. 12- History of tuberculosis infection
5. 13- History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
6. 14- Active auto-immune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroïds or immunosuppressors). Replacement therapy (e.g. thyroxine, insulin) is allowed.
7. 15- Active or history of auto-immune disease or immune deficiency (see Appendix 7 for more details)
8. 16- History of solid organ transplant nor allogenic hematopoietic stem cell transplantation
9. 17- Hypersensitivity to the active substance temozolomide or to any of the excipients listed (anhydrous lactose, colloidal anhydrous silica, sodium carboxymethyl starch type A, tartaric acid, stearic acid),
10. 18- Hypersensitivity to dacarbazine (DTIC )
11. 19- Hypersensitivity to the active substance pembrolizumab or to any of the excipients listed (L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433))
12. 2- Presence of extracranial metastasis
13. 20- Hypersensitivity to the active substance Montanide
14. 21- 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
15. 22- Inadequate hematology and organ functions; known cardiac failure or unstable coronaropathy, respiratory failure or another life threatening condition.
16. 23- Patient with unresolved non-hematologic toxicities > Grade 1 (or > Grade 2 if deemed acceptable by the investigator and not considered a safety risk )
17. 24- Major surgery within 1 month prior randomization or planned during the study
18. 3- Leptomeningeal disease on MRI
19. 4- Contrast enhancement ≥4 cm (largest diameter on axial T1 sequences) on inclusion MRI
20. 5- Previous treatment with Carmustine impregnated wafers (GliadelR)
21. 6- Previous treatment with bevacizumab or other Vascular Endothelial Growth Factor (VEGF) antagonists
22. 7- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study.
23. 8- Prior therapy with an anti-PD-1, anti-PD-L1, or with an agent directed to another immune checkpoint (e.g. CTLA-4, TIGIT, Lag3…).
24. 9- Immunosuppressive treatment including CS > 10 mg prednisone or equivalent within the previous 2 weeks
25. 25- Vaccination with alive attenuated vaccine within 4 weeks prior the first dosing. Patient must agree not to receive live attenuated vaccine including influenza vaccine during the treatment and within 6 months following the last dose of pembrolizumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. In each experimental arms, the primary endpoint for the efficacy is the rate of patients alive at 18 months post randomization

Secondary endpoints 6

1. The rate of patients alive at 18 months post randomization
2. Overall survival (OS) defined as the time interval from randomization to the date of death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period
3. Progression free survival (PFS) according to RANO 2.0 criteria: defined as the time interval from the date of randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation showing no progression during study treatment follow-up.
4. Adverse events and routine lab abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0, see Appendix 2), timing, seriousness and relationship to study treatments at each visit.
5. Immunogenecity will be assess by ex vivo IFN-γ ELISpot in peripheral blood (Adotevi JCO 2023).
6. Health related Quality of life will be evaluated with EORTC-QLQC30 questionnaire and BN20 module at randomization and at 6 months.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire

Sponsor organisation

Centre Hospitalier Regional Universitaire

Address

2 Place Saint Jacques, Cs 51804 Cs 51804

City

Besancon Cedex

Postcode

25030

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Marion JACQUIN

Public contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Sophie DEPIERRE

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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