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

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.