Re: [89Zr]Zr-Girentuximab for PET-CT Imaging of Clear-cell Renal Cell Carcinoma: A Prospective, Open-label, Multicentre, Phase 3 Trial

The prospective, open-label, multicenter, phase 3 ZIRCON trial (ClinicalTrials.gov NCT03849118) provides key data on the diagnostic accuracy of 89Zr-girentuximab positron emission tomography (PET)/computed tomography (CT) for noninvasive diagnosis of clear-cell renal cell carcinoma (ccRCC) [1]. Girentuximab, a chimeric monoclonal antibody, targets carbonic anhydrase 9, a tumor-associated antigen that is highly expressed in ccRCC. Previous phase 1/2 trials showed the favorable safety profile of 89Zr-girentuximab and its potential impact on clinical decision-making. ZIRCON enrolled patients with an indeterminate cT1 renal mass suspicious for ccRCC who were scheduled for nephrectomy at 36 research hospitals and practices across nine countries over a 3-yr period (August 2019–July 2022). Patients received a single intravenous dose of 89Zr-girentuximab (37 MBq ±10%; 10 mg of girentuximab) at 5 d (±2 d) before abdominal PET/CT imaging. Surgery was performed no later than 90 d after administration of 89Zr-girentuximab. From 371 patients screened for eligibility, 300 (80.9%) received 89Zr-girentuximab, of whom 284/300 (95%) were included in the primary analysis. Using blinded central histological confirmation (conducted by three independent readers) as the standard of truth, the study found that 89Zr-girentuximab had mean sensitivity of 85.5% (95% confidence interval [CI] 81.5–89.6%) and mean specificity of 87.0% (95% CI 81.0–93.1%) for detection of ccRCC. No safety signals were observed (most adverse events were not or were unlikely to be related to 89Zr-girentuximab, with 74% of 261 events occurring during or after surgery).