A phase I study of ABT‐510 plus bevacizumab in advanced solid tumors. (21st March 2013)

• Record Type: Journal Article
• Authors: Uronis, Hope E.; Cushman, Stephanie M.; Bendell, Johanna C.; Blobe, Gerard C.; Morse, Michael A.; Nixon, Andrew B.; Dellinger, Andrew; Starr, Mark D.; Li, Haiyan; Meadows, Kellen; Gockerman, Jon; Pang, Herbert; Hurwitz, Herbert I.
• Is Part Of: Cancer medicine. Volume 2:Number 3(2013:Jun.)
• Page Start: 316
• Page End: 324
• Publication Date: 2013-03-21
• Subjects: ABT‐510 -- advanced solid tumors -- bevacizumab -- phase I; 616.994005
• DOI: 10.1002/cam4.65
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT‐510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT‐510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma‐based biomarkers and wound angiogenesis. Thirty‐four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment‐related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D‐dimer, von Willebrand factor, placental growth factor, and stromal‐derived factor 1 in response to treatment with the combination of bevacizumab and ABT‐510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful. Abstract : This study was designed to evaluate the effects of dual inhibition of the vascular endothelial growth factor axis and the thrombospondin axis on refractory solid tumors. We found signs of clinical activity in patients with various tumor types, though whether this was related to one or both agents is not known. We also found that plasma levels of stromal‐derived factor 1 (SDF‐1) and placental growth factor (PlGF) were elevated on combination therapy, consistent with prior published reports. These data suggest that combination anti‐angiogenesis therapies may be clinically useful.