Evaluation of UCPVax Vaccine +/- Pembrolizumab Combined With Standard Treatment as Adjuvant Therapy in Patients With Unmethylated MGMT Glioblastoma

NCT07347210 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2024/8942024-514399-42-00
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 4

Brief Summary

Glioblastomas (GBM) are the most frequent brain tumors and one of the most lethal adult cancers despite maximal multimodal therapy. Despite maximal safe resection followed by radiotherapy and temozolomide (TMZ) ± tumor-treating fields, median overall survival for newly diagnosed GBM remains around 18 months and long-term survival is rare, and recurrence is nearly universal. So, the development of new therapeutic strategies is a critical unmet need in GBM. Despite the limited success of anti-PD(L)-1 therapy, immunotherapy remains a promising option in GBM. Current challenge supports to develop combinatorial therapy approaches considering the particular immune tumor microenvironment in GBM. Anticancer vaccines have shown promising signs of efficacy in GBM but critical factors challenge their efficacy. CD4 T help is of major interest for cancer vaccine effectiveness and for immune checkpoint inhibitors success. We previously designed UCPVax a CD4 T helper-targeted cancer vaccine derived from telomerase (TERT), a very attractive GBM-associated antigen (Adotévi O, J Clin Oncol 2023 ; Laheurte C, Cell Report Med 2025). The induction of robust tumor reactive CD4 T cell response with UCPVax together with TMZ-mediated immune effects will promote recruitment of effectors immune cells into tumor bed creating a more suitable microenvironment for anti-PD-1 action. This is a proof-of-concept phase II trial to evaluate the efficacy of maintenance therapy evaluating UCPVax +/- pembrolizumab combined to standard treatment in newly diagnosed unmethylated MGMT glioblastoma. A translational research network will be implemented to better understand the therapeutic efficacy of this combination.

Conditions

Primary Glioblastoma

Keywords

GBM; UCPVax; pembrolizumab; cancer vaccine; telomerase; CD4 T cell

Outcome Measures

Primary Outcomes (1)

• Assessment of the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the experimental arm with UCPVax +/- pembrolizumab combined with standard treatment (Temozolomide +/- Novo-TTF-200A)

  Rate for patients alive at 18 months post-randomization

  18 months

Secondary Outcomes (8)

• Assessment of the Overall Survival (OS) at 18 months since randomization of patients with GBM treated in the control arm receiving standard treatment( Temozolomide +/- NovoTTF-200A)

  18 months

• Assessment of the Overall Survival (OS) in the three arms

  from date of randomization until date of death from any cause, assessed up to 42 months

• Assessment of the progression free survival (PFS) since randomization in the three arms

  From date of randomization until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 42 months

• Assessment of the progression free survival (PFS) at 6 months since randomization in the three arms

  6 months

• Evaluation of incidence of treatment-emergent adverse events in the three arms

  up to 42 months

Study Arms (3)

Experimental Arm A

EXPERIMENTAL

UCPVax + Pembrolizumab + Standard of care

Drug: UCPVax; Drug: Pembrolizumab; Drug: Temozolomide

Experimental Arm B

EXPERIMENTAL

UCPVax + Standard of care

Drug: UCPVax; Drug: Temozolomide

Control Arm C

OTHER

Standard of care

Drug: Temozolomide

Interventions

UCPVax DRUG

Priming : UCPVax (two helper peptides UCP2 and UCP4 + Montanide ISA51) at 0.5 mg subcutaneously at day 1, 8, 15, 29, 36 and 43 Boost : UCPVax at 0.5 mg subcutaneously one month after priming and then every 8 weeks for 12 months maximum

Experimental Arm A; Experimental Arm B

Pembrolizumab DRUG

400 mg/m1 every 6 weeks since day 1 until disease progression or unacceptable toxicity for a maximum of 1 year

Experimental Arm A

Temozolomide DRUG

150-200 mg/m2/day x 5 days per month x 6 months according to best standard of care starting at day 1 of week 1 (with vaccine 1 of UCPVax). Additional treatment with NOVO-TTF200A will be allowed.

Control Arm C; Experimental Arm A; Experimental Arm B

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥ 18 with informed consent signed
• Patient with a confirmed histological diagnosis of non-mutated IDH primary glioblastoma (surgical resection or biopsy).
• Tumor with unmethylated MGMT promoter status
• Patients having completed the concomitant phase of radiotherapy + temozolomide regimen (standard radiotherapy with 60 Gy in 30 fractions or hypofractionated radiotherapy with 40 Gy in 15 fractions), and eligible for the 6 monthly cycles of maintenance temozolomide
• Karnofsky Perfomance status (KPS) ≥ 70%
• Life expectancy ≥ 3 months
• 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
• Adequate organ function laboratory values
• Females must be using highly effective contraceptive measures, 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 :
• Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
• 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.
• Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but tubal ligation.
• Female with childbearing potential must use effective contraception during study treatment and after the end of treatment based on the last study drug administrated: 6 months after the last dose of Temozolomide; 4 months after the last dose of pembrolizumab and 1 month after the last injection of UCPVax.
• Male patients with a female partner of childbearing potential should be willing to use barrier contraception and to refrain from donating sperm during the study and and post-treatment based on the last study drug administrated: 3 months after the last dose of temozolomide; 4 months after the last pembrolizumab dose; 1 month after the last UCPVax injection.
• Patient affiliated to or beneficiary of French social security system

You may not qualify if:

• Patients will not be eligible for this study for any of the following reasons:
• IDH1 or IDH2 mutated tumor
• Presence of extracranial metastasis
• Leptomeningeal disease on MRI
• Previous treatment with Carmustine impregnated wafers (GliadelR)
• 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.
• Non-eligible to treatment by UCPVax:
• 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…).
• Immunosuppressive treatment including CS \> 10 mg prednisone or equivalent within the previous 2 weeks
• 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.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• History of tuberculosis infection
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

CHU de Besançon

Besançon, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHU La Timone

Marseille, France

Location

Hôpital Saint-Louis - APHP

Paris, France

Location

Related Publications (2)

• Laheurte C, Boullerot L, Ndao B, Malfroy M, Queiroz L, Guillaume P, Loyon R, Seffar E, Gravelin E, Renaudin A, Jacquin M, Meurisse A, Vernerey D, Ghiringhelli F, Godet Y, Genolet R, Jandus C, Borg C, Adotevi O. UCPVax, a CD4 helper peptide vaccine, induces polyfunctional Th1 cells, antibody response, and epitope spreading to improve antitumor immunity. Cell Rep Med. 2025 Jul 15;6(7):102196. doi: 10.1016/j.xcrm.2025.102196. Epub 2025 Jun 20.

  PMID: 40543509 BACKGROUND

• Adotevi O, Vernerey D, Jacoulet P, Meurisse A, Laheurte C, Almotlak H, Jacquin M, Kaulek V, Boullerot L, Malfroy M, Orillard E, Eberst G, Lagrange A, Favier L, Gainet-Brun M, Doucet L, Teixeira L, Ghrieb Z, Clairet AL, Guillaume Y, Kroemer M, Hocquet D, Moltenis M, Limat S, Quoix E, Mascaux C, Debieuvre D, Fagnoni-Legat C, Borg C, Westeel V. Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study. J Clin Oncol. 2023 Jan 10;41(2):373-384. doi: 10.1200/JCO.22.00096. Epub 2022 Sep 7.

  PMID: 36070539 BACKGROUND

MeSH Terms

Interventions

pembrolizumab; Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Olivier ADOTEVI, MD

  University Hospital of Besançon

  PRINCIPAL INVESTIGATOR

• Antoine CARPENTIER, MD

  University Hospital of Besançon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sophie DEPIERRE

CONTACT

+33 3 81 66 81 66; sdepierre@chu-besancon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization 2:2:1

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: January 16, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)