村垣善浩 客員教授（先端工学外科学分野・脳神経外科）の論文です。
“A randomized, placebo-controlled phase III trial of an autologous, formalin-fixed tumor vaccine for newly diagnosed glioblastoma: trial protocol”
MURAGAKI Yoshihiro†, ISHIKAWA Eiichi , TAMURA Manabu*, KAWAMATA Takakazu, GOSHO Masahiko, HASHIMOTO Koichi , KOMORI Takashi, YOKOO Hideaki, MATSUTANI Masao, MAEBAYASHI Katsuya , TANAKA Toshihide, YAMAGUCHI Shigeru , KANAMORI Masayuki , YAMAMOTO Tetsuya, HANIHARA Mitsuto , ARAKAWA Yoshiki , SASAYAMA Takashi , ABE Tatsuya, NAKAMURA Hideo , MUKASA Akitake , UZUKA Takeo, NAKAJO Kosuke , OHNO Tadao
Japanese Journal of Clinical Oncology, hyaf078(2025)
Abstract
This multi-institutional, double-blind, randomized, placebo-controlled phase III trial was designed to evaluate the efficacy and safety of Cellm-001, an autologous formalin-fixed brain tumor immunostimulant, for newly diagnosed glioblastoma with gross total resection to prolong overall survival (OS) and prevent recurrence after surgery. One hundred twelve patients are to be randomized 1:1 to either Cellm-001 with standard chemoradiotherapy (CRT) or saline solution with standard CRT. Randomization is based on the following stratified randomization criteria: age, Karnofsky Performance Status, and the presence or absence of photodynamic therapy (PDT). The primary endpoint is OS and secondary outcomes are progression-free survival (PFS), OS and PFS with and without radiographically residual lesions as subgroups, OS and PFS with and without PDT, p53-negative OS and PFS, high Cluster of Differentiation-8 score OS and PFS, OS associated with death in primary disease, and 24-month OS and PFS rates. All institutions received ethical committee approval and patient enrollment began in 2021.
Importance of the study: Given the growing interest in immunotherapy (IMT), we developed an autologous formalin-fixed tumor vaccine (AFTV) manufactured from the patient’s own glioblastoma multiforme (GBM) tissue in paraffin-embedded blocks made from the resected tumor and a double-blind, randomized phase IIB trial of AFTV with temozolomide in newly diagnosed GBM was conducted. The 3-year progression-free survival (PFS) rate for patients with gross total resection (GTR) on imaging tended toward improvement: 81% in the AFTV group versus 46% in the placebo group (P = .067). Based on these IIB results, the feasibility of conducting a phase III trial was confirmed for IIB-eligible patients with total resection. We here plan to conduct the world’s first double-blind, randomized, placebo-controlled phase III trial using Cellm-001 to demonstrate autologous tumor immunostimulant efficacy. This IMT, in combination with sub-analyses (GTR, P53 status, CD8 score, and other factors) to be validated, is expected to be a breakthrough in effective standards of care for the treatment of GBM.
