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

Int J Cancer. 2017 Feb 15;140(4):973-982. doi: 10.1002/ijc.30510. Epub 2016 Nov 21.

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.

Keywords: KIF20A; adjuvant therapy; pancreatic cancer; peptide vaccine; predictive marker.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / surgery
  • Carcinoma, Pancreatic Ductal / therapy*
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Epitopes / immunology
  • Female
  • Gemcitabine
  • HLA-A24 Antigen / immunology*
  • Humans
  • Immunotherapy, Active*
  • Kaplan-Meier Estimate
  • Kinesins / immunology*
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Pancreatectomy
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / surgery
  • Pancreatic Neoplasms / 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*

Substances

  • 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