A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma

Yoshitaka Narita, Yoshiki Arakawa, Fumiyuki Yamasaki, Ryo Nishikawa, Tomokazu Aoki, Masayuki Kanamori, Motoo Nagane, Toshihiro Kumabe, Yuichi Hirose, Tomotsugu Ichikawa, Hiroyuki Kobayashi, Takamitsu Fujimaki, Hisaharu Goto, Hideo Takeshima, Tetsuya Ueba, Hiroshi Abe, Takashi Tamiya, Yukihiko Sonoda, Atsushi Natsume, Tatsuyuki KakumaYasuo Sugita, Nobukazu Komatsu, Akira Yamada, Tetsuro Sasada, Satoko Matsueda, Shigeki Shichijo, Kyogo Itoh, Mizuhiko Terasaki

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Background. We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. Methods. We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. Results. Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA− activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively. Conclusion. This phase III trial met neither the primary nor secondary endpoints.

Original languageEnglish
Pages (from-to)348-359
Number of pages12
Issue number3
Publication statusPublished - 2019 Feb 19


  • Biomarker for overall survival
  • Personalized peptide vaccine
  • Phase III trial
  • Pre-existing immunity
  • Recurrent glioblastoma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research


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