Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.

Abstract

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]