Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors

Isamu Okamoto, Tokuzo Arao, Masaki Miyazaki, Taroh Satoh, Kunio Okamoto, Takuya Tsunoda, Kazuto Nishio, Kazuhiko Nakagawa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Targeting of tumor angiogenesis with vaccines is a potentially valuable approach to cancer treatment. Elpamotide is an immunogenic peptide derived from vascular endothelial growth factor receptor 2, which is expressed at a high level in vascular endothelial cells. We have now carried out a phase I study to evaluate safety, the maximum tolerated dose, and potential pharmacodynamic biomarkers for this vaccine. Ten HLA-A*24:02-positive patients with advanced refractory solid tumors received elpamotide s.c. at dose levels of 0.5, 1.0, or 2.0 mg once a week on a 28-day cycle. Five patients experienced an injection site reaction of grade 1 and 2, which was the most frequent adverse event. In the 1.0 mg cohort, one patient experienced proteinuria of grade 1 and another patient developed both hypertension and proteinuria of grade 1. No adverse events of grade 3 or higher were observed, and the maximum tolerated dose was therefore not achieved. The serum concentration of soluble vascular endothelial growth factor receptor 2 decreased significantly after elpamotide vaccination. Microarray analysis of gene expression in PBMCs indicated that several pathways related to T cell function and angiogenesis were affected by elpamotide vaccination, supporting the notion that this peptide induces an immune response that targets angiogenesis in the clinical setting. In conclusion, elpamotide is well tolerated and our biomarker analysis indicates that this anti-angiogenic vaccine is biologically active. Clinical trial registration no. UMIN000008336.

Original languageEnglish
Pages (from-to)2135-2138
Number of pages4
JournalCancer Science
Volume103
Issue number12
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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