Telix Pharmaceuticals' investigational PET agent TLX250-CDx (Zircaix) has demonstrated high accuracy in detecting and characterizing clear cell renal cell carcinoma (ccRCC) in patients with indeterminate renal masses (IRMs), according to results from the Phase 3 ZIRCON trial published in The Lancet Oncology. This multicenter, open-label trial, involving 300 patients, suggests TLX250-CDx could significantly improve the diagnosis and management of kidney cancer.
The ZIRCON trial (NCT03849118) assessed the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC in patients with cT1 IRMs (≤7 cm) who were scheduled for nephrectomy. The results indicated a mean sensitivity of 86%, specificity of 87%, and positive predictive value of 93% across three independent radiology readers. These values exceeded pre-specified thresholds, indicating robust diagnostic performance, even for small lesions.
Impact on Clinical Practice
According to Professor Brian Shuch, Director of the Kidney Cancer Program at UCLA, current imaging techniques often fail to differentiate between benign and malignant renal lesions, leading to unnecessary surgeries in up to 30% of patients. TLX250-CDx addresses this unmet need by providing a non-invasive method to accurately detect and differentiate ccRCC, potentially reducing overtreatment and improving patient outcomes.
Safety and Efficacy
The ZIRCON trial reported a favorable safety profile for TLX250-CDx, with only two mild adverse events related to the treatment out of 263 adverse events experienced among 124 patients. The most common grade 3 or higher adverse events were post-procedural hemorrhage (2%), urinary retention (1%), and hypertension (1%), most of which occurred after surgery. The imaging can be performed 5±2 days after administration.
Regulatory Status and Future Plans
Telix is currently working to resubmit a biologics license application (BLA) to the FDA for TLX250-CDx, addressing concerns raised regarding sterility assurance during dispensing. The company anticipates completing the necessary remediations and is targeting a commercial launch in 2025. If approved, TLX250-CDx would be the first commercially available targeted PET agent specifically for kidney cancer in the United States.
Mechanism of Action
TLX250-CDx is a zirconium-89 (89Zr) radiolabeled monoclonal antibody that targets carbonic anhydrase IX (CAIX), a tumor-associated antigen highly expressed in ccRCC. This targeted approach allows for precise imaging of ccRCC lesions, improving diagnostic accuracy.
Dr. David N. Cade, Chief Medical Officer at Telix, emphasized that the ZIRCON trial results make a compelling case for TLX250-CDx as a breakthrough product for kidney cancer imaging, validating CAIX as a novel target. The high diagnostic performance of TLX250-CDx may support early and accurate diagnosis, inform patient risk stratification, and optimize clinical decision-making.
