Telix's Phase III ZIRCON Trial for Kidney Cancer Imaging Published in The Lancet Oncology

Telix Pharmaceuticals Limited, based in Melbourne, Australia, has announced significant findings from its Phase III ZIRCON trial, which have been published in The Lancet Oncology. The trial assessed the efficacy of their investigational PET agent, TLX250-CDx (Zircaix®), in identifying and characterizing clear cell renal cell carcinoma (ccRCC) in patients with indeterminate renal masses (IRMs).

Led by Professor Brian Shuch from UCLA, the prospective, open-label, multicenter Phase III trial involved 300 patients with IRMs measuring up to 7 cm. The study concluded that TLX250-CDx has a favorable safety profile and high accuracy in non-invasively detecting and characterizing ccRCC. This new imaging technique could potentially change clinical practices.

Small kidney masses are increasingly being discovered incidentally during abdominal imaging for other health issues. Current imaging methods often fail to differentiate between benign and malignant renal lesions, leading to unnecessary invasive procedures. Up to 30% of patients undergo surgeries to remove masses that turn out to be benign, while delays in diagnosing ccRCC can significantly reduce survival rates.

Professor Shuch emphasized the difficulty of assessing whether renal masses are cancerous using standard imaging technologies like CT or MRI scans. These conventional methods cannot reliably distinguish between benign and malignant renal lesions or provide insights into disease biology. This challenge highlights the need for a non-invasive technique that can accurately detect and differentiate ccRCC from other renal masses, aiding clinical decision-making. The ZIRCON trial demonstrated that TLX250-CDx can fulfill this need.

TLX250-CDx, a zirconium-89 (89Zr) radiolabeled monoclonal antibody, targets carbonic anhydrase IX (CAIX), a tumor-associated antigen highly expressed in ccRCC. The ZIRCON trial, following successful Phase I and II trials, aimed to evaluate the sensitivity and specificity of TLX250-CDx PET/CT imaging in non-invasively detecting ccRCC in patients with cT1 IRMs. These patients underwent nephrectomy, with central histological confirmation as the standard of truth.

Key findings of the ZIRCON trial include:
- 89Zr-girentuximab PET/CT imaging accurately detected ccRCC in patients with cT1 IRM, showing a mean sensitivity of 86%, specificity of 87%, and a positive predictive value of 93%.
- The imaging technique demonstrated high diagnostic performance for both small and very small renal masses.
- The trial met all primary and secondary endpoints, with robust agreement among the radiology readers and perfect intra-reader consistency.
- No safety concerns were associated with the administration of 89Zr-girentuximab.
- Imaging performed within 5±2 days after administration was sufficient to visualize and assess ccRCC lesions, offering a flexible imaging window beneficial for patient management.

Dr. David N. Cade, Chief Medical Officer at Telix, highlighted the trial's results as a compelling case for TLX250-CDx as a breakthrough product for kidney cancer imaging. The high diagnostic performance, including for very small lesions, supports early and accurate diagnosis, aiding patient risk stratification and clinical decision-making, potentially reducing over- and under-treatment.

If approved by the U.S. Food and Drug Administration (FDA), TLX250-CDx would be the first targeted PET agent specifically for kidney cancer to be available commercially in the U.S.

Telix Pharmaceuticals Limited is a biopharmaceutical company focusing on developing and commercializing therapeutic and diagnostic radiopharmaceuticals. The company is headquartered in Melbourne, Australia, with international operations in the U.S., Europe, and Japan. Telix is developing a portfolio of products to address significant unmet medical needs in oncology and rare diseases.