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Published on: April 15, 2016
Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors
Andrew J Brenner1, Yael C Cohen, Eyal Breitbart
1Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, Texas, USA.
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 × 10(10) (cohort 1) to 1 × 10(13) (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 × 10(11) 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 × 10(13) VPs. Evidence of transgene expression in tumor tissue and tumor response was observed.
Insights
VB-111, an antiangiogenic gene therapy, demonstrated safety and tolerability in patients with advanced solid tumors. Evidence of transgene expression and tumor response was observed in this Phase I study.
Area of Science:
- Oncology
- Gene Therapy
- Cancer Research
Background:
- VB-111 is an antiangiogenic agent utilizing a modified adenovirus vector (Ad-5) to induce tumor vasculature apoptosis.
- It expresses a Fas-chimera transgene in angiogenic endothelial cells via a specific promoter.
Purpose of the Study:
- To evaluate the pharmacokinetics, pharmacodynamics, safety, and efficacy of VB-111.
- To assess the maximum tolerated dose of VB-111 in patients with advanced solid tumors.
Main Methods:
- A Phase I, dose-escalation study involving single intravenous infusions of VB-111.
- Doses escalated from 1 × 10(10) to 1 × 10(13) viral particles (VP).
- Included assessments of pharmacokinetic and pharmacodynamic profiles, tumor response, and overall survival.
Main Results:
- VB-111 was safe and well-tolerated up to 1 × 10(13) VP.
- Self-limited fever and chills occurred at doses >3 × 10(11) VP.
- Transgene expression was detected in tumor tissue, and one partial response was observed in a patient with papillary thyroid carcinoma.
Conclusions:
- VB-111 is safe and well-tolerated as a single administration in advanced metastatic cancer patients.
- Evidence of transgene expression in tumor tissue and tumor response supports further investigation.
