Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4535
© 2006 American Society of Clinical Oncology

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Abstract

Phase II study of volociximab (M200), an 5ß1 anti-integrin antibody in refractory metastatic clear cell renal cell cancer (RCC)

UCLA, Los Angeles, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; PDL BioPharma, Fremont, CA; Cleveland Clinic Taussig Cancer Center, Cleveland, OH

4535

Background: Blocking angiogenesis has been shown to be an effective strategy for controlling tumor growth in RCC. Tumor angiogenesis occurs when pro-angiogenic growth factors are released, stimulating endothelial cell proliferation and migration to form neovessels. M200 is an IgG4 chimeric monoclonal antibody that targets 5ß1, thereby inducing apoptosis of proliferating endothelial cells. M200 activity is independent of growth factor stimulus, suggesting that binding of fibronectin to 5ß1 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, single cohort pilot phase II study of 40 patients (pts) with RCC. Pts received no more than 2 prior regimens. Pts received M200 10 mg/kg IV every 2 weeks until disease progression. Pts were evaluated for efficacy every 8 weeks by objective response using RECIST criteria. An independent data safety monitoring board was utilized to review safety data. Results: A total of 40 pts were enrolled. All pts were evaluable for safety and 37 pts for objective response (to date). Median age was 62.8 years. ECOG score was 0 in 27 (67.5%) and 1 in 13 (32.5%) pts. Prior nephrectomy occured in 39 (97%) pts. Other prior treatment included IL-2 in 15 (37.5%), interferon alpha in 6 (15%), IL-2 + interferon in 2 (5%) pts. Most frequent side effects were fatigue 37.5%, nausea 15% and hypertension 7.5%. Five pts died in the study, four with progressive disease (PD) and 1 with arrhythmia (unrelated to M200). SD was observed in 32/37 (87%) of pts. No changes in hematological, renal and hepatic parameters were noted. Median time to progression was 113+ days. The average peak and trough concentrations of circulating M200 following 6 weeks of treatment were 390 µg/mL and 140 µg/mL, respectively. There were no detectable immune responses to M200. Conclusions: M200 is well tolerated at 10 mg/kg Q2W. Stable disease is noted in 87% of pts. Follow-up continues. A higher dose level is being evaluated.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PDL BioPharma Abbott, Antigenics, GlaxoSmithKline, Pfizer Bayer, Genentech, GlaxoSmithKline, Pfizer, Wyeth Bayer, Celgene, Genentech, GlaxoSmithKline, Memorial Sloan-Kettering Cancer Center, PDL BioPharma, Pfizer, UCLA, Wyeth

Abstract presentation from the 2006 ASCO Annual Meeting