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
Department of Medical Device Engineering, Kobe University, Kusunoki-cho, Chuo-ku, Kobe City, Hyogo 650-0017, Japan.
Department of Neurosurgery, Tokyo Women's Medical University, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Jpn J Clin Oncol. 2025 May 16. doi: 10.1093/jjco/hyaf078.
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.
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.
Registry number: jRCT2031200153; Date of Registration: 20 /October, /2020; Date of First Patient Enrollment: 14 /January/, 2021.
本多机构、双盲、随机、安慰剂对照的III期试验旨在评估自体福尔马林固定脑肿瘤免疫刺激剂Cellm-001对新诊断的胶质母细胞瘤患者在进行大体全切术后延长总生存期（OS）和预防术后复发的疗效及安全性。112例患者将按1:1随机分为接受Cellm-001联合标准放化疗（CRT）组或生理盐水联合标准CRT组。随机分组基于以下分层随机标准：年龄、卡氏功能状态以及是否接受光动力疗法（PDT）。主要终点是总生存期，次要结局包括无进展生存期（PFS）、按有无影像学残留病灶作为亚组的总生存期和无进展生存期、按有无PDT的总生存期和无进展生存期、p53阴性患者的总生存期和无进展生存期、高分化簇8评分患者的总生存期和无进展生存期、与原发性疾病死亡相关的总生存期，以及24个月的总生存期和无进展生存率。所有机构均获得伦理委员会批准，患者入组于2021年开始。
鉴于对免疫疗法（IMT）的兴趣日益增加，我们研发了一种自体福尔马林固定肿瘤疫苗（AFTV），它由患者自身多形性胶质母细胞瘤（GBM）组织制成，取自切除肿瘤的石蜡包埋块，并对新诊断的GBM患者进行了AFTV联合替莫唑胺的双盲、随机IIB期试验。影像学显示为大体全切（GTR）的患者3年无进展生存期（PFS）率有改善趋势：AFTV组为81%，安慰剂组为46%（P = 0.067）。基于这些IIB期结果，对于符合IIB期标准且已全切的患者进行III期试验的可行性得到了证实。我们在此计划开展世界上首个使用Cellm-001的双盲、随机、安慰剂对照III期试验，以证明自体肿瘤免疫刺激剂的疗效。这种免疫疗法，结合有待验证的亚组分析（GTR、P53状态、CD8评分及其他因素），有望成为GBM治疗有效护理标准的一项突破。
注册号：jRCT2031200153；注册日期：2020年10月20日；首例患者入组日期：2021年1月14日。
