The increasing detection of renal masses presents a significant dilemma as conventional tools (e.g., CT, MRI, biopsy) have limitations. Accurate noninvasive techniques to risk stratify patients with renal mass remains an unmet need.
Girentuximab is a chimeric monoclonal antibody with high affinity for carbonic anhydrase IX (CAIX), which is highly expressed in clear cell renal carcinoma (ccRCC); thus, 89Zr-DFO-girentuximab (TLX250‑CDx) may aid differentiation of ccRCC and other renal lesions. ZIRCON (NCT03849118) was an open label, multicenter clinical trial evaluating the performance of TLX250-CDx PET/CT for detection of ccRCC in patients with indeterminate renal masses (IDRM).
300 patients with an IDRM (≤7 cm; cT1) who were scheduled for partial or radical nephrectomy within 90 days from planned TLX250-CDx administration received a single dose of TLX250‑CDx IV (37 MBq±10%; 10 mg girentuximab) on Day 0 and underwent abdominal PET/CT imaging on Day 5 (±2 days). Blinded central histology review determined ccRCC status and CAIX expression; PET positivity was assessed by 3 independent blinded central readers. The coprimary objectives were to evaluate both the sensitivity and specificity of TLX250‑CDx PET/CT imaging in detecting ccRCC, using histology as the standard of truth. Key secondary objectives included both sensitivity and specificity in the subgroup of patients with IDRM ≤4 cm (cT1a). Other secondary objectives included positive/negative predictive values, accuracy, safety, and tolerability.
300 patients received TLX250-CDx (mean age 62±12 y; 71% Male). Of 288 patients with central histopathology assessment, 67% had ccRCC, and 62% had CT1a. The primary analysis included 284 evaluable patients (central histology and readable PET). Across all 3 readers, the 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%] resp. for key secondary. For all evaluable patients, positive and negative predictive values were ≥91.7% and ≥73.7%, respectively, and accuracy >85.6%. The optimal SUVmax threshold to distinguish the ccRCC from other lesions was ≥24.1, based on Youden index. PET+ ccRCC had higher mean CAIX expression compared with PET‑ ccRCC patients (p<0.05). Of 11 PET+ patients who were ccRCC negative on central histopathology assessment, 9 had papillary RCC, and 1 each had sarcoma and oncocytoma. Of 263 adverse events (AEs) in 124 patients, 2 AEs of mild intensity were treatment related.
ZIRCON study confirms TLX250-CDx PET/CT is a well-tolerated and accurate modality for noninvasive identification of ccRCC in IDRM. This tool could be included into the diagnostic/management of patients with IDRM, limiting biopsies or unnecessary treatment of benign lesions.
Telix sponsored this study. Stefanie Martina (Telix) provided writing support.