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

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.