Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)

Toni K. Choueiri; Yousef Zakharia; Sumanta Pal; Judit Kocsis; Russell Pachynski; Alexandr Poprach; Andrew B. Nixon; Yingmiao Liu; Mark Starr; Jing Lyu; Kouros Owzar; Mollie deShazo; Primo Lara; Lajos Geczi; Thai H. Ho; Meghara Walsh; Bonne Adams; Liz Robertson; Mohamed Darif; Charles Theuer; Neeraj Agarwal

doi:10.1002/onco.13777

Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)

Toni K. Choueiri, Yousef Zakharia, Sumanta Pal, Judit Kocsis, Russell Pachynski, Alexandr Poprach, Andrew B. Nixon, Yingmiao Liu, Mark Starr, Jing Lyu, Kouros Owzar, Mollie deShazo, Primo Lara, Lajos Geczi, Thai H. Ho, Meghara Walsh, Bonne Adams, Liz Robertson, Mohamed Darif, Charles TheuerNeeraj Agarwal

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

Abstract

Lessons Learned: The combination of carotuximab with axitinib did not provide a benefit over axitinib monotherapy in patients with metastatic clear cell renal cell carcinoma who had previously progressed on one or more vascular endothelial growth factor (VEGF)-targeted therapies. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Background: Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors. This study evaluated an antiendoglin monoclonal antibody (carotuximab, TRC105) combined with axitinib in patients with advanced or metastatic clear cell renal cell carcinoma (mccRCC) who had progressed following one or more prior VEGF inhibitors. Methods: TRAXAR was a multicenter, international randomized 1:1 (stratified by ECOG, 0 vs. 1), phase II study of carotuximab combined with axitinib versus axitinib alone in mccRCC patients who had progressed following one or more prior VEGF inhibitors. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR) per RECIST 1.1. Results: A total of 150 patients were randomized. The combination therapy resulted in shorter median PFS by RECIST 1.1 than axitinib monotherapy (6.7 vs. 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Conclusion: The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.

Original language	English (US)
Pages (from-to)	560-e1103
Journal	Oncologist
Volume	26
Issue number	7
DOIs	https://doi.org/10.1002/onco.13777
State	Published - Jul 2021

Keywords

Axitinib
Carotuximab
Endoglin
Phase II
Renal cell cancer
TRAXAR
TRC105

ASJC Scopus subject areas

General Medicine

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10.1002/onco.13777

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Choueiri, T. K., Zakharia, Y., Pal, S., Kocsis, J., Pachynski, R., Poprach, A., Nixon, A. B., Liu, Y., Starr, M., Lyu, J., Owzar, K., deShazo, M., Lara, P., Geczi, L., Ho, T. H., Walsh, M., Adams, B., Robertson, L., Darif, M., ... Agarwal, N. (2021). Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR). Oncologist, 26(7), 560-e1103. https://doi.org/10.1002/onco.13777

Choueiri, TK, Zakharia, Y, Pal, S, Kocsis, J, Pachynski, R, Poprach, A, Nixon, AB, Liu, Y, Starr, M, Lyu, J, Owzar, K, deShazo, M, Lara, P, Geczi, L, Ho, TH, Walsh, M, Adams, B, Robertson, L, Darif, M, Theuer, C & Agarwal, N 2021, 'Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)', Oncologist, vol. 26, no. 7, pp. 560-e1103. https://doi.org/10.1002/onco.13777

@article{1f960e62100b4fdebba7fd23017810a3,

title = "Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)",

abstract = "Lessons Learned: The combination of carotuximab with axitinib did not provide a benefit over axitinib monotherapy in patients with metastatic clear cell renal cell carcinoma who had previously progressed on one or more vascular endothelial growth factor (VEGF)-targeted therapies. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Background: Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors. This study evaluated an antiendoglin monoclonal antibody (carotuximab, TRC105) combined with axitinib in patients with advanced or metastatic clear cell renal cell carcinoma (mccRCC) who had progressed following one or more prior VEGF inhibitors. Methods: TRAXAR was a multicenter, international randomized 1:1 (stratified by ECOG, 0 vs. 1), phase II study of carotuximab combined with axitinib versus axitinib alone in mccRCC patients who had progressed following one or more prior VEGF inhibitors. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR) per RECIST 1.1. Results: A total of 150 patients were randomized. The combination therapy resulted in shorter median PFS by RECIST 1.1 than axitinib monotherapy (6.7 vs. 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Conclusion: The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.",

keywords = "Axitinib, Carotuximab, Endoglin, Phase II, Renal cell cancer, TRAXAR, TRC105",

author = "Choueiri, {Toni K.} and Yousef Zakharia and Sumanta Pal and Judit Kocsis and Russell Pachynski and Alexandr Poprach and Nixon, {Andrew B.} and Yingmiao Liu and Mark Starr and Jing Lyu and Kouros Owzar and Mollie deShazo and Primo Lara and Lajos Geczi and Ho, {Thai H.} and Meghara Walsh and Bonne Adams and Liz Robertson and Mohamed Darif and Charles Theuer and Neeraj Agarwal",

note = "Publisher Copyright: {\textcopyright} AlphaMed Press; the data published online to support this summary are the property of the authors.",

year = "2021",

month = jul,

doi = "10.1002/onco.13777",

language = "English (US)",

volume = "26",

pages = "560--e1103",

journal = "Oncologist",

issn = "1083-7159",

publisher = "AlphaMed Press",

number = "7",

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TY - JOUR

T1 - Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)

AU - Choueiri, Toni K.

AU - Zakharia, Yousef

AU - Pal, Sumanta

AU - Kocsis, Judit

AU - Pachynski, Russell

AU - Poprach, Alexandr

AU - Nixon, Andrew B.

AU - Liu, Yingmiao

AU - Starr, Mark

AU - Lyu, Jing

AU - Owzar, Kouros

AU - deShazo, Mollie

AU - Lara, Primo

AU - Geczi, Lajos

AU - Ho, Thai H.

AU - Walsh, Meghara

AU - Adams, Bonne

AU - Robertson, Liz

AU - Darif, Mohamed

AU - Theuer, Charles

AU - Agarwal, Neeraj

N1 - Publisher Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

PY - 2021/7

Y1 - 2021/7

N2 - Lessons Learned: The combination of carotuximab with axitinib did not provide a benefit over axitinib monotherapy in patients with metastatic clear cell renal cell carcinoma who had previously progressed on one or more vascular endothelial growth factor (VEGF)-targeted therapies. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Background: Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors. This study evaluated an antiendoglin monoclonal antibody (carotuximab, TRC105) combined with axitinib in patients with advanced or metastatic clear cell renal cell carcinoma (mccRCC) who had progressed following one or more prior VEGF inhibitors. Methods: TRAXAR was a multicenter, international randomized 1:1 (stratified by ECOG, 0 vs. 1), phase II study of carotuximab combined with axitinib versus axitinib alone in mccRCC patients who had progressed following one or more prior VEGF inhibitors. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR) per RECIST 1.1. Results: A total of 150 patients were randomized. The combination therapy resulted in shorter median PFS by RECIST 1.1 than axitinib monotherapy (6.7 vs. 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Conclusion: The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.

AB - Lessons Learned: The combination of carotuximab with axitinib did not provide a benefit over axitinib monotherapy in patients with metastatic clear cell renal cell carcinoma who had previously progressed on one or more vascular endothelial growth factor (VEGF)-targeted therapies. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Background: Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors. This study evaluated an antiendoglin monoclonal antibody (carotuximab, TRC105) combined with axitinib in patients with advanced or metastatic clear cell renal cell carcinoma (mccRCC) who had progressed following one or more prior VEGF inhibitors. Methods: TRAXAR was a multicenter, international randomized 1:1 (stratified by ECOG, 0 vs. 1), phase II study of carotuximab combined with axitinib versus axitinib alone in mccRCC patients who had progressed following one or more prior VEGF inhibitors. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR) per RECIST 1.1. Results: A total of 150 patients were randomized. The combination therapy resulted in shorter median PFS by RECIST 1.1 than axitinib monotherapy (6.7 vs. 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pretreatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels. Conclusion: The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.

KW - Axitinib

KW - Carotuximab

KW - Endoglin

KW - Phase II

KW - Renal cell cancer

KW - TRAXAR

KW - TRC105

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ER -

Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR)

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