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Conference Paper: Biomarker modulation in patients (pts) receiving TRC105 (T) and bevacizumab (B) in a phase Ib clinical trial

TitleBiomarker modulation in patients (pts) receiving TRC105 (T) and bevacizumab (B) in a phase Ib clinical trial
Authors
Issue Date2014
PublisherLippincott Williams & Wilkins.
Citation
The 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO 2014), Chicago, IL., 30 May-3 June 2014. In Journal of Clinical Oncology, 2014, v. 32 n. 15 suppl., abstract no. 11020 How to Cite?
AbstractBACKGROUND: Endoglin (END; CD105) is a membrane-bound cell surface receptor expressed on proliferating endothelial cells implicated in resistance to VEGF inhibition. T, an anti-End monoclonal antibody, potentiates anti-VEGF therapy in in vitro and in vivo models. The combination of T plus B was well tolerated and was active in pts who progressed on prior B treatment. METHODS: Pts with advanced refractory solid tumors were treated with escalating doses of T plus B. Pts received 1 week of B monotherapy prior to the addition of T. Thirty-eight biomarkers related to tumor growth, angiogenesis, and inflammation were analyzed using an optimized multiplex ELISA platform. Samples from 38 pts were collected at baseline (BL), 1 week (C1D8), 2 week (C1D15), 4 week (C2D1), and end of study (EOS). Biomarker concentrations on study were compared to baseline using the Wilcoxon signed rank test with statistical significance assumed at p<0.05. RESULTS: After 1 week of B monotherapy (C1D8), PlGF was elevated and ANG-2, soluble END (sEND), TSP2, and VEGFR1 were decreased. Following the addition of T, only Ang-2 remained significantly decreased, while the following analytes were significantly elevated at C1D15, C2D1 and EOS: CRP, sEND, E-Selectin, IL-6, PAI-1 (active and total), P-Selectin, SDF-1, TGF-b1, and VCAM-1. Increases in sEND and PlGF are consistent with observations from pts treated with either T or B alone, respectively. The inflammatory markers, CRP and IL-6, and TGFb-regulated proteins, PAI-1 active and sEND, all exhibited greater than a 5-fold increase on average at EOS. Interestingly, the elevation of the END ligand, TGFb1, in response to T plus B treatment, has not been observed in pts treated with either agent alone. CONCLUSIONS: Treatment of pts with either T or B alone is associated with modulation of multiple angiogenic and inflammatory biomarkers. However, the combination of both agents led to increases in many inflammatory and TGFb-related proteins that persisted throughout the study. The differences across the biomarker patterns from pts treated with T plus B suggest increased bioactivity for the combination and support the role of T potentiating anti-VEGF therapies in pts.
DescriptionThis journal suppl. entitled: 2014 ASCO Annual Meeting Abstracts
Persistent Identifierhttp://hdl.handle.net/10722/207683
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_US
dc.contributor.authorClarke, Jen_US
dc.contributor.authorStarr, MDen_US
dc.contributor.authorBrady, JCen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorRushing, Cen_US
dc.contributor.authorAlvarez, Den_US
dc.contributor.authorAdams, BJen_US
dc.contributor.authorTheuer, CPen_US
dc.contributor.authorHurwitz, Hen_US
dc.contributor.authorNixon, ABen_US
dc.date.accessioned2015-01-14T08:35:44Z-
dc.date.available2015-01-14T08:35:44Z-
dc.date.issued2014en_US
dc.identifier.citationThe 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO 2014), Chicago, IL., 30 May-3 June 2014. In Journal of Clinical Oncology, 2014, v. 32 n. 15 suppl., abstract no. 11020en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/207683-
dc.descriptionThis journal suppl. entitled: 2014 ASCO Annual Meeting Abstracts-
dc.description.abstractBACKGROUND: Endoglin (END; CD105) is a membrane-bound cell surface receptor expressed on proliferating endothelial cells implicated in resistance to VEGF inhibition. T, an anti-End monoclonal antibody, potentiates anti-VEGF therapy in in vitro and in vivo models. The combination of T plus B was well tolerated and was active in pts who progressed on prior B treatment. METHODS: Pts with advanced refractory solid tumors were treated with escalating doses of T plus B. Pts received 1 week of B monotherapy prior to the addition of T. Thirty-eight biomarkers related to tumor growth, angiogenesis, and inflammation were analyzed using an optimized multiplex ELISA platform. Samples from 38 pts were collected at baseline (BL), 1 week (C1D8), 2 week (C1D15), 4 week (C2D1), and end of study (EOS). Biomarker concentrations on study were compared to baseline using the Wilcoxon signed rank test with statistical significance assumed at p<0.05. RESULTS: After 1 week of B monotherapy (C1D8), PlGF was elevated and ANG-2, soluble END (sEND), TSP2, and VEGFR1 were decreased. Following the addition of T, only Ang-2 remained significantly decreased, while the following analytes were significantly elevated at C1D15, C2D1 and EOS: CRP, sEND, E-Selectin, IL-6, PAI-1 (active and total), P-Selectin, SDF-1, TGF-b1, and VCAM-1. Increases in sEND and PlGF are consistent with observations from pts treated with either T or B alone, respectively. The inflammatory markers, CRP and IL-6, and TGFb-regulated proteins, PAI-1 active and sEND, all exhibited greater than a 5-fold increase on average at EOS. Interestingly, the elevation of the END ligand, TGFb1, in response to T plus B treatment, has not been observed in pts treated with either agent alone. CONCLUSIONS: Treatment of pts with either T or B alone is associated with modulation of multiple angiogenic and inflammatory biomarkers. However, the combination of both agents led to increases in many inflammatory and TGFb-related proteins that persisted throughout the study. The differences across the biomarker patterns from pts treated with T plus B suggest increased bioactivity for the combination and support the role of T potentiating anti-VEGF therapies in pts.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.en_US
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titleBiomarker modulation in patients (pts) receiving TRC105 (T) and bevacizumab (B) in a phase Ib clinical trialen_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume32en_US
dc.identifier.issue15 suppl. (May 20 Supplement)en_US

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