TY - JOUR
T1 - Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer
T2 - VENUS-PC study
AU - Suzuki, Nobuaki
AU - Hazama, Shoichi
AU - Iguchi, Haruo
AU - Uesugi, Kazuhiro
AU - Tanaka, Hiroaki
AU - Hirakawa, Kosei
AU - Aruga, Atsushi
AU - Hatori, Takashi
AU - Ishizaki, Hidenobu
AU - Umeda, Yuzo
AU - Fujiwara, Toshiyoshi
AU - Ikemoto, Tetsuya
AU - Shimada, Mitsuo
AU - Yoshimatsu, Kazuhiko
AU - Shimizu, Ryoichi
AU - Hayashi, Hiroto
AU - Sakata, Koichiro
AU - Takenouchi, Hiroko
AU - Matsui, Hiroto
AU - Shindo, Yoshitaro
AU - Iida, Michihisa
AU - Koki, Yasunobu
AU - Arima, Hideki
AU - Furukawa, Hiroyuki
AU - Ueno, Tomio
AU - Yoshino, Shigefumi
AU - Nakamura, Yusuke
AU - Oka, Masaaki
AU - Nagano, Hiroaki
N1 - Funding Information:
The authors thank Otsuka Pharmaceutical Co., Ltd. and OncoTherapy Science, Inc. for their excellent advice and cooperation and or providing all of the peptides and the IFA. We thank Ms. Yoshie Takeuchi, Yoshiko Fukahori, and Atsuko Kaneta for their excellent clinical research coordination. The authors also thank Professor Hiroyuki Suzuki, Department of Regenerative Surgery, Fukushima Medical University, Professor Koji Kono, Department of Surgery, National University of Singapore and Professor Kenzaburo Tani, Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation Kyushu University for their excellent management as The Data and Safety Monitoring Committee of this study. Grant sponsor of this study was Ministry of Health Labor, and Welfare of Japan Grant Number H23-cancer-010, and this study was supported partially by the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), The Japan Agency for Medical Research and Development (AMED).
Publisher Copyright:
© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
AB - We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
KW - Advanced pancreatic cancer
KW - CTL
KW - immunotherapy
KW - peptide cocktail
KW - phase II
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UR - http://www.scopus.com/inward/citedby.url?scp=85007018116&partnerID=8YFLogxK
U2 - 10.1111/cas.13113
DO - 10.1111/cas.13113
M3 - Article
C2 - 27783849
AN - SCOPUS:85007018116
SN - 1347-9032
VL - 108
SP - 73
EP - 80
JO - Cancer Science
JF - Cancer Science
IS - 1
ER -
