A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine [hVEGF.sub.26-104]/RFASE in Patients with Advanced Solid Malignancies

Background. Targeting vascular endothelial growth factor-A (VEGF) is a well-established anticancer therapy. We designed a first-in-human clinical trial to investigate the safety and immunogenicity of the novel vaccine [hVEGF.sub.26-104]/RFASE. Methods. Patients with advanced solid malignancies with...

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Bibliographic Details
Published in:The oncologist (Dayton, Ohio) Ohio), 2021-02, Vol.26 (2), p.e218
Main Authors: Goedegebuure, Ruben S.A, Wentink, Madelon Q, van der Vliet, Hans J, Timmerman, Peter, Griffioen, Arjan W, de Gruijl, Tanja D, Verheul, Henk M.W
Format: Article
Language:English
Subjects:
Amino acids
Cancer
Care and treatment
Clinical trials
Complications and side effects
Endothelium
Evaluation
Fatty acids
Health aspects
Medical research
Medicine, Experimental
Patient outcomes
Peptides
Product development
Vaccines
Vascular endothelial growth factor
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Summary:Background. Targeting vascular endothelial growth factor-A (VEGF) is a well-established anticancer therapy. We designed a first-in-human clinical trial to investigate the safety and immunogenicity of the novel vaccine [hVEGF.sub.26-104]/RFASE. Methods. Patients with advanced solid malignancies with no standard treatment options available were eligible for this phase I study with a 3+3 dose-escalation design. On days 0, 14, and 28, patients received intramuscular [hVEGF.sub.26-104], a truncated synthetic three-dimensional (3D)-structured peptide mimic covering the amino acids 26-104 of the human [VEGF.sub.165] isoform, emulsified in the novel adjuvant Raffinose Fatty Acid Sulphate Ester (RFASE), a sulpholipopolysaccharide. Objectives were to determine safety, induction of VEGF-neutralizing antibodies, and the maximum tolerated dose. Blood was sampled to measure VEGF levels and antibody titers. Results. Eighteen of 27 enrolled patients received three immunizations in six different dose-levels up to 1,000 [micro]g [hVEGF.sub.26-104] and 40 mg RFASE. No dose-limiting toxicity was observed. Although in four patients an antibody titer against [hVEGF.sub.26-104] was induced (highest titer: 2.77 [sup.10]log), neither a reduction in VEGF levels nor neutralizing antibodies against native [VEGF.sub.165] were detected. Conclusion. Despite having an attractive safety profile, [hVEGF.sub.26-104]/RFASE was not able to elicit seroconversions against native [VEGF.sub.165] and, consequently, did not decrease circulating VEGF levels. Deficient RFASE adjuvant activity, as well as dominant immunoreactivity toward neoepitopes, may have impeded [hVEGF.sub.26-104]/RFASE's efficacy in humans. The Oncologist 2021;26:e218-e229 Key Words. Angiogenesis inhibitors * Peptite vaccine * Vascular Endothelial Growth Factor A
ISSN:1083-7159
1549-490X
DOI:10.1002/onco.13576