Introduction: The increasing detection of renal masses (RM) presents a significant dilemma as conventional tools (eg, CT, MRI, biopsy) have limitations. Approximately 25% of patients with RM <4cm undergo unnecessary surgery. Accurate noninvasive techniques to risk stratify patients with RM remains an unmet need. Girentuximab is a monoclonal antibody that targets carbonic anhydrase IX (CAIX), an enzyme highly expressed in clear cell renal carcinoma (ccRCC). Radiolabeled 89Zr-DFO-girentuximab can aid differentiation between ccRCCs and other renal lesions. ZIRCON (NCT03849118) evaluated the performance of 89Zr-DFO-girentuximab PET/CT for detection of ccRCC in patients with indeterminate RM (IDRM). Methods: In this open label trial, patients with an IDRM (=7cm; stage cT1), scheduled for partial or radical nephrectomy within 90 days from planned 89Zr-DFO-girentuximab dosing, were eligible. Enrolled patients received a single dose IV (37 MBq±10%; 10mg girentuximab) on Day 0 and underwent abdominal PET/CT on Day 5 (±2d). Blinded central histology review determined ccRCC status. Coprimary objectives were to evaluate both the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC in patients with IDRM, using histology as standard of truth. Key secondary objectives included sensitivity and specificity of 89Zr-DFO-girentuximab PET/CT in patients with IDRM =4cm (cT1a). Other objectives included assessment of safety and tolerability, and suspected secondary lesions; the latter was investigated as per institutional protocols. Results: 300 patients (mean age 62±12 y; 71% Male) received 89Zr-DFO-girentuximab. Of 288 patients with central histopathology assessment, 67% had ccRCC, and 62% had CT1a masses. The primary analysis included 284 patients. Across all 3 readers, average [95% CI] sensitivity and specificity was 86% [80%, 90%] and 87% [79%, 92%] respectively for coprimary endpoints, and 85% [77%, 91%] and 90% [79%, 95%] respectively for key secondary. Of 11 PET+ patients who were ccRCC- on central histopathology, 9 had papillary RCC, and 1 each had sarcoma and oncocytoma. Renal masses were classified as Bosniak I, II, IIF, III, and IV in 7 (2.5%), 9 (3.2%), 8 (2.8%), 65 (22.9%), and 192 (67.6%) patients, respectively. Of 263 adverse events (AEs) in 124 patients, 2 treatment-related AEs of mild intensity were reported. Conclusions: 89Zr-DFO-girentuximab PET/CT is well tolerated and can accurately and noninvasively identify and characterize IDRMs, showing promising utility for guiding surgical and treatment decisions. SOURCE OF Funding: Telix Pharmaceuticals
