Phase I and pharmacokinetic study of etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors

This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alpha(v)beta(3) integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg. The mean number of weekly infusions was 19 (ranging 5-53). Frequently reported adverse events were grades 1-2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49-180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials.