Phase i dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors

Andrew J. Brenner, Yael C. Cohen, Eyal Breitbart, Livnat Bangio, John Sarantopoulos, Francis J. Giles, Ernest C. Borden, Dror Harats, Pierre L. Triozzi

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Purpose: VB-111 is an antiangiogenic agent consisting of a nonreplicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a Fas-chimera transgene in angiogenic endothelial cells. In a phase I dose-escalation study, pharmacokinetics, pharmacodynamics, safety, and efficacy of a single dose of VB-111 in patients with advanced solid tumors were evaluated. Experimental Design: VB-111 was administered as a single i.v. infusion at escalating doses from 1×1010 (cohort 1) to 1 × 1013 (cohort 7) viral particles (VP) in successive cohorts. Assessments included pharmacokinetic and pharmacodynamic profiles, tumor response, and overall survival. Results: Thirty-three patients were enrolled. VB-111 was safe and well-tolerated; self-limited fever and chills were seen at doses above 3 × 1011 VPs. Transgene expression was not detected in blood but was detected in an aspirate from a subcutaneous metastasis after treatment. One patient with papillary thyroid carcinoma had a partial response. Conclusions: VB-111 was safe and well tolerated in patients with advanced metastatic cancer at a single administration of up to 1 × 1013 VPs. Evidence of transgene expression in tumor tissue and tumor response was observed.

Original languageEnglish (US)
Pages (from-to)3996-4007
Number of pages12
JournalClinical Cancer Research
Volume19
Issue number14
DOIs
StatePublished - Jul 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Brenner, A. J., Cohen, Y. C., Breitbart, E., Bangio, L., Sarantopoulos, J., Giles, F. J., Borden, E. C., Harats, D., & Triozzi, P. L. (2013). Phase i dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors. Clinical Cancer Research, 19(14), 3996-4007. https://doi.org/10.1158/1078-0432.CCR-12-2079