My Criminalized Truth Over Docetaxel E7080 Posted By An Older Specialist

Recently, a one armed variant of the anti c MET antibody 5D5, MetMAb, was developed to avoid agonistic activity that can occur when divalent antibodies bind and crosslink MET receptors. MetMAb binds to the Sema domain of c MET, a region which is critical for binding HGF.

Treatment of the orthotopic model of U87 and G55 tumors with MetMAb significantly inhibited growth E7080 only in SF/HGF activated tumors. In addition, in MetMAb treated tumors, cell proliferation was reduced more than 75%, microvessel density was reduced more than 90% and apoptosis was increased more than 60%. In a c MET and HGF expressing, autocrine driven, human KP4 pancreatic cancer orthotopic model, MetMAb also significantly inhibited c MET phosphorylation, with a concomitant decrease in tumor growth and improvement in survival. The combination of MetMAb with bevacizumab was tested in a phase I study which consisted of three parts: 3 t 3 dose escalation of MetMAb evaluating 1, 4, 10, 15, 20, and 30 mg/kg intravenously every 3 weeks, expansion at 15 mg/kg intravenously every 3 weeks, and combination of MetMAb at 10 and 15 mg/kg plus bevacizumab 15 mg/kg intravenously every 3 weeks.

CR was observed in one patient with gastric E7080 carcinoma after four cycles of single agent MetMAb. The combination of MetMAb with bevacizumab was safe and well tolerated. A phase II trial of MetMAb in combination with bevacizumab plus paclitaxel in patients with triple negative breast cancer is currently ongoing. In a randomized, double blind phase II study, MetMAb 15 mg/kg intravenously plus erlotinib was compared with erlotinib plus placebo in 128 patients with advanced NSCLC. The study included patients with all histologies following at least one chemotherapy containing regimen for stage IIIB/ IV disease. Patients in the control arm had the option of being unblinded and crossing over to receive MetMAb after disease progression. Immunohistochemistry was performed for c MET in 121 patients.

A trend for overall survival benefit in these patients was also seen with MetMAb plus erlotinib.