Anti-telomerase vaccine in patients with newly diagnosed, unmethylated MGMT glioblastoma: A phase II study.

Medientyp: E-Artikel

Titel: Anti-telomerase vaccine in patients with newly diagnosed, unmethylated MGMT glioblastoma: A phase II study

Beteiligte: Carpentier, Antoine F; Verlut, Clotilde; Ghiringhelli, François; Bronnimann, Charlotte; Ursu, Renata; Fumet, Jean David; Gherga, Elisabeta; Lefort, Felix; Belin, Catherine; Vernerey, Dewi; Hervieu, Alice; Laheurte, Caroline; Meurisse, Aurelia; Jacquin, Marion; Malfroy, Marine; Fagnoni-Legat, Christine; Lehmann-Che, Jacqueline; Boullerot, Laura; Cuzzubbo, Stefania; Adotevi, Olivier

Erschienen: American Society of Clinical Oncology (ASCO), 2023

Sprache: Englisch

DOI: 10.1200/jco.2023.41.16_suppl.2005

ISSN: 0732-183X; 1527-7755

Schlagwörter: Cancer Research ; Oncology

Entstehung:

Anmerkungen:

Beschreibung: 2005 Background: TERT, a subunit of the telomerase complex, is largely expressed in almost all cancers. Among those cancers, glioblastomas (GBM) harbor the highest incidence of activating mutations within the TERT promoter (over 85% of patients). This high incidence underlies the potential role of TERT in oncogenesis, and points out TERT as a highly relevant tumor target in GBM. UCPvax is a therapeutic vaccine composed of two CD4 helper peptides derived from TERT, combined with the montanide adjuvant. We conducted a phase IIa trial to test the immunogenicity, safety and efficacy of UCPvax in patients with newly diagnosed GBM. Methods: Key inclusion criteria were: histologically confirmed, non-mutated IDH1 glioblastoma, unmethylated MGMT promoter status, previous treatment with concomitant radiotherapy and temozolomide (TMZ), Karnofsky Performance status (KPS) ≥ 70%, steroids < 10mg/ day equivalent prednisone, and lymphocytes count ≥ 0.8 x 109/L. One month after completion of radiation/TMZ, patients started UCPvax vaccinations on days 1, 8, 15, 29, 36 and 43, then every two months until tumor progression, without additional cure of TMZ. Peripheral blood mononuclear cells were collected before treatment, at 1 and 2 months after treatment and, at each vaccination boost. The primary endpoint was an anti-TERT specific CD4 T-cell response measured ex vivo in peripheral blood using IFN-gamma ELISPOT at 2 months. Secondary endpoints included safety, overall survival (OS) and progression-free survival (PFS). Results: Thirty-one adult patients (median age 60-yr old, median KPS 90%) were included in this study. All patients received at least one vaccination, and vaccinations were given for 4.5 months on average (min 2– max 14). At baseline, only one patient had a pre-existing anti-TERT CD4 T-cell response (3%). After immunizations, de novo induction and/or amplification of an anti-TERT response were found in 29/30 pts (97%). An epitope spread response against other tumor-associated antigens was detected in 12/25 pts (48%). No severe (grade 3–4) toxicity was attributable to the vaccination. All patients developed local skin reactions (≤ grade 2), 16 patients complained of transient asthenia (≤grade 2), and 13 patients experienced local pain (≤grade 2). In the intent-to-treat population (n=31), the PFS was 8.9 months (95% CI: 7.6–10.6) and the median OS was 17.9 months (95% CI: 16–23). Two years after diagnosis, 26 % of the patients were still alive. OS was significantly improved in the patients developing an epitope spread response vs the others (19.3 vs 15.8 months, respectively, p=0.03). Conclusions: UCPVax is highly immunogenic and provides an interesting OS rate in this population of poor prognosis, unmethylated MGMT GBM patients. These data support further clinical studies of UCPvax in GBM patients. Clinical trial information: NCT04280848 .

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: