A Randomized Phase 2 Trial of Axitinib/Nivolumab Combination Therapy vs Single Agent Axitinib or Nivolumab for the Treatment of TFE/Translocation Renal Cell Carcinoma (tRCC) Across All Age Groups

National Cancer Institute (NCI)
Study Design: 
This phase 2, randomized, multicenter, open-label trial (ECOG AREN1721) is enrolling patients with histologically confirmed unresectable or metastatic tRCC of patients age >1 years, as long as Body Surface Area is >0.53 m2. Patients may not have received VEGF-targeted therapies or anti-PD-1 or anti-PD-L1 antibodies, but other therapies are allowed. Patients will be randomized to 1 of 3 arms, receiving either axitinib and nivolumab (Arm A), axitinib alone (Arm B), or nivolumab alone (Arm C). Patients will be treated to progression or until 2 years if there is disease control. A total of 4 years of follow-up is planned.
Translocation Renal Cell Carcinomas (tRCC), characterized by Xp11.2 translocation or TFE3 gene fusions, represent a rare subset of metastatic RCC with a poor prognosis. Patients tend to present at a younger age, and while rare in adults, tRCC represent about half of all pediatric RCCs. Historically, patients with this RCC subtype have highly aggressive disease, which tends to be refractory to typical RCC therapies. However, there are no formal treatment recommendations for this disease, and previously, no prospective trials had been conducted to study this subtype.
The primary endpoint of the trial is PFS. Antitumor immune response and stability of T cell activation will be studied in an exploratory fashion. The study will also study the clinical behavior for up to 4 years of translocation morphology renal cell carcinoma.
This study is the first prospective trial studying patients with tRCC, and will require awareness and participation from all oncologists treating genitourinary malignancies to successfully accrue. While the study will undoubtedly include a large pediatric cohort, adult patients also need to be studied to see if clinical behavior and response to therapies are similar. The study may help to better elucidate the pathophysiology of this particular subtype to better explain its aggressive behavior. It may also contribute to our understanding of response or lack of response to targeted and immune checkpoint therapies for this patient population.