Phase 1 Dose-Escalation Study of VB-111, an Anti-Angiogenic Virotherapy, in Patients with Advanced Solid Tumors
Mené sur 33 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la toxicité et diverses caractéristiques pharmacocinétiques et pharmacodynamiques d'une dose unique d'une virothérapie anti-angiogénique, VB-111
Purpose: VB-111 is an anti-angiogenic agent consisting of a non-replicating 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 was evaluated. Experimental Design:VB-111 was administered as a single intravenous infusion at escalating doses from 1x1010 (cohort 1) to 1x1013 (cohort 7) viral particles (VPs) 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 3x1011 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 partial response. Conclusions: VB-111 was safe and well tolerated in patients with advanced metastatic cancer at a single administration of up to 1x1013 VPs. Evidence of transgene expression in tumor tissue and tumor response was observed.