A multicenter, open-label phase Ib/II study to assess the safety and clinical activity of intravenous combretastatin A1 diphosphate (OXi4503) as monotherapy in subjects with primary or secondary hepatic tumor burden

TPS164 Background: Combretastatin A1 diphosphate (CA1P, OXi4503) is a novel vascular disrupting agent (VDA) that is a reversible tubulin-binding agent with direct cytotoxic activity when bioactivated to its reactive orthoquinone metabolite. Several oxidative enzymes have been shown to catalyze this reaction including myeloperoxidase (MPO), tyrosinase, and hepatic peroxidases. Based on these findings it is expected that OXi4503 should be more active in tissues and tumors containing high levels of these and other oxidative enzymes. Nonclinical blood flow studies in tumor-bearing SCID mice showed that OXi4503 treatment (1 to 50 mg/kg) produced a decrease in tumor-associated blood volume. A dose of 50 mg/kg resulted in approximately 100% reduction in tumor vascular volume, compared with control mice. Tumor growth inhibition has been observed in single- and repeat-dose xenograft studies in multiple tumor models including breast cancer (MDA-MB-231), colorectal, renal (Caki-1), hepatocellular (HEP-G2), melanoma ...