title: Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
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.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Kunio
authors.initials: K
authors.lastname: Okamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D059871:HLA-A24 Antigen / Q000378:metabolism; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; D022223:Vaccines, Subunit; C578462:arginyl-phenylalanyl-valyl-prolyl-aspartyl-glycyl-asparagyl-arginyl-isoleucine; D040301:Vascular Endothelial Growth Factor Receptor-2