Final results from phase II study of volociximab, an α5β1 anti-integrin antibody, in refractory or relapsed metastatic clear cell renal cell carcinoma (mCCRCC)

5094 Background: A critical survival step for proliferating endothelial cells is the ligation of fibronectin in the extracellular matrix to integrin a5β1. Voloxicimab, a chimeric monoclonal antibody, blocks fibronectin binding to a5β1, and induces apoptosis of proliferating endothelial cells. Voloxicimab activity is independent of growth factor stimulus, suggesting that a5β1 signalling occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, phase II study in mCCRCC. Patients (pts) received volociximab 10 mg/kg IV every 2 weeks until disease progression. Pts were evaluated for efficacy every 8 weeks using RECIST criteria. Results: A total of 40 pts were enrolled. All pts were evaluable for safety and efficacy. Median time since first diagnosis was 2.5 years. ECOG score was 0–1 in all pts. Prior nephrectomy occurred in 38 (95%) pts. Nineteen (47.5%) pts had ≥ 2 prior therapy. Twenty one (52.5 %) pts had prior anti agiogenic therapy. Other prior treatment included IL-2 in 15 (37.5%), interferon alpha in 7 (17.5 %), IL-2 + interferon in 2 (5%) pts. Most frequent side effects were fatigue in 27 (67.5%) pts, nausea 14 (35%) pts, dyspnoea 8 (20%) pts and arthralgia 7 (17.5%) pts, of which none were grade 3 or 4. Seven (17.5%) pts had SAEs. Stable disease (SD) was observed in 32 (80 %) pts including 1 confirmed PR. Duration of SD ranged from 2–22 months (mo). Fourteen (35%) pts had time to progression (TTP) between 5.8 to 22 mo: Four (10%) pts had TTP ≥ 14 mo (range 14- 22 mo), 8 (20%) pts had TTP ≥ 6 mo (range 6- 12 mo) and 2 (5%) pts had TTP = 5.8 mo. Median TTP was 4 mo. Median overall survival (OS) has not been reached after 22 mo. OS at 6 mo was 79% and 68% at 22 mo. Six (15%) pts died in the study, 5 (12.5%) pts due to progressive disease and 1 with arrhythmia (unrelated to volociximab). Conclusions: Volociximab is well tolerated at 10 mg/kg q2w. Stable disease is noted in 80 % of pts. Based on clinical activity, a randomized controlled trial is being planned. No significant financial relationships to disclose.