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Conference Paper: Modulation of angiogenic biomarkers in patients receiving high-dose TRC105

TitleModulation of angiogenic biomarkers in patients receiving high-dose TRC105
Authors
Issue Date2012
PublisherLippincott Williams & Wilkins.
Citation
The 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO 2012), Chicago, IL., 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 suppl., abstract no. e21038 How to Cite?
AbstractBACKGROUND: TRC105, an anti-CD105 monoclonal antibody, has completed phase 1 testing and is being studied in multiple phase 2 trials. We previously reported that low dose TRC105 (0.01-1.0 mg/kg) modulated the expression of soluble angiogenic biomarkers in patients [J Clin Oncol 29: 2011 (suppl; abstr 10565)]. In this report, we evaluated angiogenic biomarkers in patients receiving higher doses of TRC105 including the recommended phase 2 dose. METHODS: Patients with advanced refractory solid tumors were treated with escalating doses of TRC105 until disease progression. Serial plasma samples were analyzed via an optimized multiplex ELISA platform. 36 biomarkers related to tumor growth, angiogenesis, and inflammation were assayed at baseline (BL), after 1 month (C2D1), concurrent with radiological restaging near the end of cycle 2 (C2D22), and at end of study (EOS). RESULTS: 32 patients treated with TRC105 at doses of 0.3 to 15 mg/kg were evaluated for biomarker expression. Wilcoxon signed rank tests indicated that the following analytes were significantly different at C2D1 when compared with baseline (p<0.05): Ang-2, IGFBP-3, total PAI-1, PDGF-AA, PDGF-BB, TSP-1, VEGF-D were all down-regulated; and E-Cadherin, soluble CD105, E-Selectin, IL-6, OPN, TSP-2, vWF were all up-regulated. At EOS, significant increases from C2D1 were observed for the following analytes: Ang-2, CRP, ICAM-1, IGFBP-1, IL-6, TSP-2, and VCAM-1 (p<0.05). Additionally, dose-dependent increases in soluble CD105 at C2D1 were observed (p<0.0001, r=0.9), suggesting direct target modulation by TRC105. CONCLUSIONS: TRC105 therapy is associated with early down-regulation of certain key angiogenic biomarkers and a dose-dependent increase in sCD105. Increases in many initially down-regulated angiogenic factors were observed at the time of progression, suggesting possible mechanisms for acquired resistance to TRC105. Further analysis of TRC105 in specified patient populations is underway and may provide more insight into the biological effects of this drug.
Persistent Identifierhttp://hdl.handle.net/10722/195795
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_US
dc.contributor.authorStarr, Men_US
dc.contributor.authorBrady, JCen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorDellinger, Aen_US
dc.contributor.authorLeigh, BRen_US
dc.contributor.authorTheuer, CPen_US
dc.contributor.authorHurwitz, Hen_US
dc.contributor.authorNixon, ABen_US
dc.date.accessioned2014-03-10T04:53:31Z-
dc.date.available2014-03-10T04:53:31Z-
dc.date.issued2012en_US
dc.identifier.citationThe 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO 2012), Chicago, IL., 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 suppl., abstract no. e21038en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/195795-
dc.description.abstractBACKGROUND: TRC105, an anti-CD105 monoclonal antibody, has completed phase 1 testing and is being studied in multiple phase 2 trials. We previously reported that low dose TRC105 (0.01-1.0 mg/kg) modulated the expression of soluble angiogenic biomarkers in patients [J Clin Oncol 29: 2011 (suppl; abstr 10565)]. In this report, we evaluated angiogenic biomarkers in patients receiving higher doses of TRC105 including the recommended phase 2 dose. METHODS: Patients with advanced refractory solid tumors were treated with escalating doses of TRC105 until disease progression. Serial plasma samples were analyzed via an optimized multiplex ELISA platform. 36 biomarkers related to tumor growth, angiogenesis, and inflammation were assayed at baseline (BL), after 1 month (C2D1), concurrent with radiological restaging near the end of cycle 2 (C2D22), and at end of study (EOS). RESULTS: 32 patients treated with TRC105 at doses of 0.3 to 15 mg/kg were evaluated for biomarker expression. Wilcoxon signed rank tests indicated that the following analytes were significantly different at C2D1 when compared with baseline (p<0.05): Ang-2, IGFBP-3, total PAI-1, PDGF-AA, PDGF-BB, TSP-1, VEGF-D were all down-regulated; and E-Cadherin, soluble CD105, E-Selectin, IL-6, OPN, TSP-2, vWF were all up-regulated. At EOS, significant increases from C2D1 were observed for the following analytes: Ang-2, CRP, ICAM-1, IGFBP-1, IL-6, TSP-2, and VCAM-1 (p<0.05). Additionally, dose-dependent increases in soluble CD105 at C2D1 were observed (p<0.0001, r=0.9), suggesting direct target modulation by TRC105. CONCLUSIONS: TRC105 therapy is associated with early down-regulation of certain key angiogenic biomarkers and a dose-dependent increase in sCD105. Increases in many initially down-regulated angiogenic factors were observed at the time of progression, suggesting possible mechanisms for acquired resistance to TRC105. Further analysis of TRC105 in specified patient populations is underway and may provide more insight into the biological effects of this drug.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.en_US
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titleModulation of angiogenic biomarkers in patients receiving high-dose TRC105en_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume30en_US
dc.identifier.issue15 suppl. (May 20 Supplement)-
dc.publisher.placeUnited Statesen_US

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