Glioblastoma (GBM) is a poor prognosis malignant grade IV glioma. After surgical resection, standard therapy consists of concomitant radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Multiple phase I/II trials and at least 3 meta-analysis showed improved survival (OS) and progression free survival (PFS) with dendritic cell (DC) vaccination in high-grade gliomas (HGGs) patients (pts). In those developing antitumor immunity, DC vaccine increases the amount of intratumoral activated cytotoxic T lymphocytes and decreases the number of FoxP3 positive regulatory T cells. Based on these data we have developed a phase II study with DC vaccine concomitant to standard RT-CT in pts undergoing radical surgery for GBM.
This is a single-arm, monocentric, phase II trial evaluating progression free-survival (PFS) and safety of a DC vaccination integrated to standard therapy in resected GBM. All pts receive a DC vaccine loaded with autologous tumor homogenate for up to one year. The vaccine administration starts at the end of the RT-CT (Induction Phase) and then is alternated to TMZ (Maintenance Phase). Primary end points are PFS and safety, among secondary end points the in vitro (Elispot, Plasma Cytokines, Tumor tissue analysis) and in vivo (DTH skin test) immune response biomarkers are evaluated. A Simon's two-stage design has been used for the sample size calculation. In the first stage, 9 pts will be accrued and a total of 28 pts will be enrolled.
The first 9 pts have been enrolled since October 2021, 4 females and 5 males with a median age of 58 years. Four pts had no MGMT methylation. Eight out of 9 pts concluded the induction phase and 1 is ongoing. To date 4 pts have progressed with a median PFS from the date of diagnosis of 7.5 months (range 5-11). DTH test became positive in 4 out of 7 evaluable pts. No gr3-4 vaccine related toxicities have been observed and gr1-2 toxicities were mostly due to local skin reactions.
This combination therapy seems very well tolerated. The 2 end points of the first step have been reached so the study will proceed to enrol the remaining 19 pts.
EudraCT 2020-003755-15.
Ridolfi Laura.
Has not received any funding.
All authors have declared no conflicts of interest.