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Conference Paper: Modulation of angiogenic biomarkers in patients treated on a phase I study of TRC105 (anti-CD105 antibody) monotherapy for advanced solid tumors

TitleModulation of angiogenic biomarkers in patients treated on a phase I study of TRC105 (anti-CD105 antibody) monotherapy for advanced solid tumors
Authors
Issue Date2011
PublisherLippincott Williams & Wilkins.
Citation
The 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 3-7 June 2011. In Journal of Clinical Oncology, 2011, v. 29 n. 15 suppl., abstract no. 10565 How to Cite?
AbstractBACKGROUND: CD105 (endoglin) is an important mediator of tumor angiogenesis that is upregulated by hypoxia and VEGF inhibitors. TRC105 is an anti-CD105 monoclonal antibody currently being evaluated in clinical trials as an anti-angiogenic cancer therapy. METHODS: In this first-in-human phase I study, pts with advanced, incurable solid tumors were treated with escalating doses of TRC105, iv every 2 wks, until disease progression. Serial plasma samples were analyzed via a novel multiplex ELISA platform optimized for cancer patients. 39 candidate biomarkers related to tumor growth, angiogenesis, and inflammation were assayed at baseline (BL), after 1 month, and at end of study (EOS). RESULTS: 19 pts treated with TRC105 at 0.01-1 mg/kg were evaluable for biomarker analysis. Spearman’s rank correlation coefficients were calculated for pairs of analytes with known interactions. Wilcoxon signed rank tests indicated that the following analytes were significantly down-regulated at one month when compared with baseline: IGFBP-3 (p=0.001), VEGF-C (p=0.002), VEGF-D (p=0.003), FGFb (p=0.008), PDGF-AA (p=0.011), PDGF-BB (p=0.039), and PIGF (p=0.045). By EOS, significant increases from the 1 month nadir were observed for the following analytes: VEGF-C (p=0.027), VEGF-D (p=0.034), and IGFBP-3 (p=0.043). CONCLUSIONS: This is the first systematic investigation of the effect(s) of TRC105 on angiogenic biomarkers in the clinical setting. Multiplex analyses indicate that TRC105 therapy is associated with down-regulation of key modulators of angiogenesis that later increase at the time of disease progression. Based on these preliminary findings, additional analyses are planned for pts treated at higher TRC105 doses as well as pts treated on phase Ib and phase II studies of TRC105 in combination with VEGF inhibitors and other standard-of-care cancer therapies.
DescriptionThis journal suppl. entitled: ASCO Meeting Abstracts Part 1
Persistent Identifierhttp://hdl.handle.net/10722/195796
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.authorPang, HMHen_US
dc.contributor.authorMarcello, Jen_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.issued2011en_US
dc.identifier.citationThe 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 3-7 June 2011. In Journal of Clinical Oncology, 2011, v. 29 n. 15 suppl., abstract no. 10565en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/195796-
dc.descriptionThis journal suppl. entitled: ASCO Meeting Abstracts Part 1-
dc.description.abstractBACKGROUND: CD105 (endoglin) is an important mediator of tumor angiogenesis that is upregulated by hypoxia and VEGF inhibitors. TRC105 is an anti-CD105 monoclonal antibody currently being evaluated in clinical trials as an anti-angiogenic cancer therapy. METHODS: In this first-in-human phase I study, pts with advanced, incurable solid tumors were treated with escalating doses of TRC105, iv every 2 wks, until disease progression. Serial plasma samples were analyzed via a novel multiplex ELISA platform optimized for cancer patients. 39 candidate biomarkers related to tumor growth, angiogenesis, and inflammation were assayed at baseline (BL), after 1 month, and at end of study (EOS). RESULTS: 19 pts treated with TRC105 at 0.01-1 mg/kg were evaluable for biomarker analysis. Spearman’s rank correlation coefficients were calculated for pairs of analytes with known interactions. Wilcoxon signed rank tests indicated that the following analytes were significantly down-regulated at one month when compared with baseline: IGFBP-3 (p=0.001), VEGF-C (p=0.002), VEGF-D (p=0.003), FGFb (p=0.008), PDGF-AA (p=0.011), PDGF-BB (p=0.039), and PIGF (p=0.045). By EOS, significant increases from the 1 month nadir were observed for the following analytes: VEGF-C (p=0.027), VEGF-D (p=0.034), and IGFBP-3 (p=0.043). CONCLUSIONS: This is the first systematic investigation of the effect(s) of TRC105 on angiogenic biomarkers in the clinical setting. Multiplex analyses indicate that TRC105 therapy is associated with down-regulation of key modulators of angiogenesis that later increase at the time of disease progression. Based on these preliminary findings, additional analyses are planned for pts treated at higher TRC105 doses as well as pts treated on phase Ib and phase II studies of TRC105 in combination with VEGF inhibitors and other standard-of-care cancer therapies.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.en_US
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titleModulation of angiogenic biomarkers in patients treated on a phase I study of TRC105 (anti-CD105 antibody) monotherapy for advanced solid tumorsen_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume29en_US
dc.identifier.issue15 suppl. (May 20 Supplement)-
dc.publisher.placeUnited Statesen_US

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