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

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 VEGF-targeted therapies. Exploratory evaluation of pre-treatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels.

Endoglin is an angiogenic receptor expressed on proliferating tumor vessels and RCC stem cells that is implicated as a mechanism of resistance to VEGFR inhibitors. This study evaluated an anti-endoglin 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.

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 versus 11.4 months). The combination was tolerated similarly to axitinib monotherapy, and there were no treatment related deaths. Exploratory evaluation of pre-treatment circulating biomarkers suggested the combination might benefit patients who have low baseline VEGF levels.

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.

The oncologist. 2021 Apr 07 [Epub ahead of print]

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

Dana-Farber Cancer Institute, Boston, Massachusetts, USA., University of Iowa, Holden Comprehensive Cancer Center, Iowa City, Iowa, USA., City of Hope National Medical Center, Duarte, California, USA., Bács-Kiskun County Hospital, Oncoradiology Center, Kecskemét, Hungary., Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA., Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Brno, Czech Republic., Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA., Graduate Group in Biostatistics, University of California Davis, Davis, California, USA., Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA., Division of Hematology/Oncology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., University of California, Davis Medical Center, Sacramento, California, USA., Országos Onkológiai Intézet, Budapest, Hungary., Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, Arizona, USA., TRACON Pharmaceuticals, Inc., San Diego, California, USA., Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.