Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105

Molecular Cancer Therapeutics
Yingmiao LiuAndrew B Nixon

Abstract

TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when ...Continue Reading

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Citations

Aug 5, 2020·Molecular Cancer Therapeutics·Yingmiao LiuAndrew B Nixon
Apr 26, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mark J A SchoonderwoerdLukas J A C Hawinkels
Dec 31, 2020·International Journal of Molecular Sciences·Yingmiao LiuLukas J A C Hawinkels
Apr 3, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·John B Pawlak, Gerard C Blobe
Feb 18, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew J ArmstrongSusan Halabi

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