ESMO 2019: Results of the Phase 2 TRAXAR Study: A Randomized Phase 2 Trial of Axitinib and TRC105 (TRAX) versus Axitinib Alone in Patients with Advanced or mRCC

Barcelona, Spain (UroToday.com) Endoglin is an essential angiogenic receptor expressed on proliferating tumor vessels and renal cell carcinoma (RCC) stem cells that is implicated as a mechanism of VEGF resistance. TRC105 is an endoglin monoclonal antibody that potentiates the anti-tumor activity of VEGF inhibitors in preclinical models1 and demonstrated a 29% RECIST response rate when combined with axitinib in patients with mRCC in a Phase 1b trial. At the ESMO 2019 annual congress, Dr. Toni Choueiri and colleagues presented results of the phase II TRAXAR study.

TRAXAR was a multicenter, randomized 1:1 (stratified by ECOG 0 vs. 1), phase 2 study of TRAX vs axitinib in patients with mRCC who had progressed following one prior VEGF inhibitor at 33 centers in the US and European Union. The primary endpoint was progression-free survival (PFS) assessed by RECIST by independent review committee. Secondary endpoints included overall response rate (ORR), and safety. PFS and ORR were also assessed by investigator review and according to Choi criteria.

ESMO_TRAX_trial.png

There were 150 patients included in TRAXAR, including 75 in the TRAX arm and 75 in the axitinib arm. Among these patients, 106 (71%) were male, 142 (95%) were white, and the median age was 64 years (range 38-82). Treatment with TRAX did not prolong PFS compared to axitinib (independent review committee: HR 1.42, 95% CI 0.88-2.30):

ESMO2019_TRAX_PFS.png

Furthermore, there was no difference in the ORR based on independent review committee (OR 1.04, 95% CI 0.50-2.15), investigator review (OR 1.19, 95% CI 0.58-2.44), or Choi criteria (OR 0.96, 95% CI 0.47-1.96). Most all-grade common adverse events in TRAX vs axitinib were headache (65.8% vs. 16.2%), epistaxis (63.0% vs. 8.1%), and diarrhea (60.3% vs. 59.5%). The most common serious adverse events included anemia (6.9% vs. 1.4%) and dehydration (4.1% vs. 0%).

Dr. Choueiri concluded with the following take home messages regarding the TRAXAR study:

  • TRC105 did not demonstrate activity when combined with axitinib in patients with mRCC who had received prior VEGF inhibitor treatment, whether assessed using RECIST or Choi criteria
  • Post-hoc analysis did not reveal a demographic or clinical characteristic associated with TRC105 in RCC
  • TRAX was generally well tolerated in patients with advanced or metastatic RCC
Clinical trial identification

NCT01806064.

Presented by: Toni K. Choueiri, MD, Jerome and Nancy Kohlberg Professor of Medicine, Harvard Medical School, Attending Physician, Solid Tumor Oncology, Dana-Farber Cancer Institute, Director, Genitourinary (GU) Oncology Disease, Center, Dana-Farber Cancer Institute, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept - 1 Oct 2019 in Barcelona, Spain

References:
1. Liu Y, Tian H, Blobe GC, et al. Effects of the combination of TRC105 and bevacizumab on endothelial cell biology. Invest New Drugs 2014;Oct;32(5):851-859.

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