No abstract

No abstract

No abstract

4549 Background: A critical survival step for proliferating endothelial cells is the ligation of fibronectin in the extracellular matrix to integrin a5β1. Volociximab, a chimeric monoclonal antibody, blocks fibronectin binding to a5β1, and induces apoptosis of proliferating endothelial cells. Volociximab activity is independent of growth factor stimuli, suggesting that a5β1 signalling occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. The efficacy and safety of volociximab in combination with GEM was determined in pts with MPC. Methods: This is a multi-center, open-label, 2-cohort, single-arm Phase II study. Eligible pts had confirmed MPC, no prior chemotherapy for MPC, adequate hematologic, renal and hepatic function, and had measurable disease. Pts received volociximab 10mg/kg iv every 2 weeks (days 1 and 15) with GEM (1,000 mg/m2 iv) on days 1, 8, 15 of a 4- week cycle until disease progression (PD). Radiologic assessments of measurable disease were performed every 8 weeks. The primary endpoint was objective tumor response (RECIST criteria). Sample size was 20 pts per cohort. At least 1 confirmed response at 4 months (mo) or SD ≥ 4 mo was necessary in cohort 1 (n=20) before expansion to the second cohort. Results: 20 pts (male=11, female=9), median age = 59.8 years (range 34–74), were treated in cohort 1 and were evaluable for safety and efficacy. PS (ECOG) was 0–1 (n=19; 95%) or 2 (n=1; 5%). Pts received a median of 8 weeks’ (range 2–58) treatment. Most frequent toxicities included nausea in 14 (70%) pts, vomiting (12; 60%) and constipation (10; 50%). Overall response included 1 confirmed PR (5%), and stable disease in 10 (50%) pts. Median time to progression was 4.3 mo; 41% had not progressed at 6 mo. Overall survival was 5.4 mo, and at 6 and 8 mo was 45%, and 37% at 12 mo. 12 pts died in the study due to PD (10 pts), GI perforation (1), pulmonary embolism (1). Conclusions: Volociximab is well tolerated at 10mg/kg 2-weekly with GEM. Cohort 2 is currently recruiting at a higher dose of volociximab (15 mg/kg) administered weekly. [Table: see text]