CVX-045: A novel antiangiogenic CovX-Body™ that potentiates targeted therapy in preclinical colon cancer models.

A18 CVX-045, the product of a chemical fusion of a recombinant humanized monoclonal antibody and two anti-angiogenic peptides, is the first in a unique class of fusion proteins. In single dose pharmacokinetic studies, the elimination half-life of CVX-045 increased as test species increased in size. CVX-045 had the longest half-life (T½) in monkeys (80 hr) followed by the rat (65 hr) and the mouse (50 hr). Anti-tumor activity of CVX-045 was evaluated in A549, A431, and HT-29 human xenograft models. Cells were implanted subcutaneously in female nu/nu mice, and tumors were staged to 300-400 mm3 prior to initiation of weekly treatments. CVX-045 (10 mg/kg) significantly reduced A549 and A43I tumor growth 73% (day 49) and 51 % (day 22), respectively, but was not effective in the HT-29 xenograft (10 or 30 mg/kg). CVX-045 demonstrated significant anti-angiogenic activity, reducing tumor microvessel density 51% in A549, 49% in A431, and 36% in HT-29 xenografts. Co-treatment with CVX-045 (30 mg/kg) plus oral sunitinib (15 mg/kg) decreased HT-29 tumor growth rate significantly (p