Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients.

Abstract

We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1-20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.

• Authors: Motoki Miyazawa, Masahiro Katsuda, Hiroyuki Maguchi, Akio Katanuma, Hiroshi Ishii, Masato Ozaka, Kenji Yamao, Hiroshi Imaoka, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Hiroki Yamaue
• Journal: International journal of cancer (Int J Cancer) Vol. 140 Issue 4 Pg. 973-982 (02 15 2017) ISSN: 1097-0215 [Electronic] United States
• PMID: 27861852 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2016 UICC.

Chemical References

• Antimetabolites, Antineoplastic
• Cancer Vaccines
• Epitopes
• HLA-A*24:02 antigen
• HLA-A24 Antigen
• KIF20A protein, human
• Neoplasm Proteins
• OCV-C01
• Peptide Fragments
• Vaccines, Subunit
• Deoxycytidine
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2
• Kinesins
• Gemcitabine

Topics

• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (therapeutic use)
• Cancer Vaccines (immunology, therapeutic use)
• Carcinoma, Pancreatic Ductal (immunology, surgery, therapy)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Epitopes (immunology)
• Female
• HLA-A24 Antigen (immunology)
• Humans
• Immunotherapy, Active
• Kaplan-Meier Estimate
• Kinesins (immunology)
• Male
• Middle Aged
• Neoplasm Proteins (immunology)
• Pancreatectomy
• Pancreatic Neoplasms (immunology, surgery, therapy)
• Peptide Fragments (immunology)
• T-Cell Antigen Receptor Specificity
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccines, Subunit (therapeutic use)
• Vascular Endothelial Growth Factor Receptor-1 (immunology)
• Vascular Endothelial Growth Factor Receptor-2 (immunology)
• Gemcitabine