Melbourne (Australia) | 11 September 2024

Telix today announces that primary results from its Phase III ZIRCON[1] trial have been published in The Lancet Oncology, reporting that Telix’s first-in-class investigational PET[2] agent, TLX250-CDx (Zircaix®[3], 89Zr-girentuximab), is highly accurate in detecting and characterising clear cell renal cell carcinoma (ccRCC) in patients with indeterminate renal masses (IRMs).

In this peer-reviewed manuscript, Professor Brian Shuch (University of California, Los Angeles, UCLA) and colleagues report results from this prospective, open-label, multicentre, Phase III trial in which 300 patients with an IRM ≤7cm (cT1) received TLX250-CDx. Authors conclude that TLX250-CDx “has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of ccRCC, which has the potential to be practice changing.”

Authors explain that small masses in the kidney are increasingly being detected incidentally when patients undergo abdominal imaging, often for other health conditions, contributing to “an era of gross overtreatment”. Diagnosis and treatment are limited by current imaging techniques, and renal mass biopsy is invasive, which can often lead to complications. Up to 30% of patients undergo unnecessary surgery, removing masses that are later determined to be benign[4]. If confirmed, however, ccRCC is the most common and aggressive form of kidney cancer, and delays in diagnosis can significantly reduce survival rates.

Professor Brian Shuch, MD, Director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at UCLA Institute of Urologic Oncology, and a ZIRCON principal investigator, said, “Until now, assessing whether renal masses are cancerous has been difficult and often involves invasive surgery or percutaneous biopsy. This is because standard imaging technology – either a CT or MRI scan – cannot reliably differentiate between benign or malignant renal lesions or provide information about disease biology.

“The challenges and uncertainty in diagnosing ccRCC underscore a critical unmet need for a new, non-invasive technique that accurately detects and differentiates ccRCC from other renal masses in patients, to inform clinical decision making. The ZIRCON trial has shown that TLX250-CDx is a breakthrough technology that can address this need.”

TLX250-CDx is a zirconium-89 (89Zr) radiolabelled monoclonal antibody that targets carbonic anhydrase IX (CAIX), a tumour-associated antigen highly expressed in ccRCC. Following successful Phase I and II trials to establish safety and preliminary efficacy, the ZIRCON trial was designed to assess sensitivity and specificity of TLX250-CDx PET/CT imaging to non-invasively detect ccRCC in patients with cT1 IRMs (≤7 cm in diameter) who underwent nephrectomy, using central histological confirmation as standard of truth.

Key findings of the ZIRCON trial, outlined in the paper, include:

  • 89Zr-girentuximab PET/CT imaging accurately detected ccRCC in patients with cT1 IRM (≤7cm), demonstrating a mean sensitivity of 86%, specificity of 87% and positive predictive value of 93%
  • 89Zr-girentuximab PET/CT imaging has high diagnostic performance for detection and characterisation of small and very small renal masses
  • The primary and secondary endpoints were met by all three radiology readers and exceeded pre-specified thresholds. Inter-reader variability indicated robust agreement among the readers and intra-reader variability was 100%, indicating perfect agreement
  • No safety concerns associated with the administration of 89Zr-girentuximab were revealed
  • Imaging performed 5±2 days after administration is sufficient to visualise and assess ccRCC lesions, with the flexible imaging window offering several advantages for patient management
  • The non-invasive nature of this technique may be especially beneficial to those at risk of complications from a surgical renal mass biopsy.

Dr David N. Cade, Chief Medical Officer at Telix said, “The results of the ZIRCON trial make a compelling case for TLX250-CDx as a breakthrough product for kidney cancer imaging, and validate CAIX as a novel target to accurately identify renal cell carcinoma.

“Professor Shuch and his co-investigators, at 36 sites worldwide, found that its high diagnostic performance, including for very small lesions, may support early and accurate diagnosis, inform patient risk stratification and clinical decision making, and reduce over- and under-treatment. We believe this result will lead to improved patient outcomes”.

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

The full paper can be found at: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00402-9/fulltext

TLX250-CDx has not received a marketing authorisation in any jurisdiction.

[1] Zirconium in Renal Cancer Oncology, ClinicalTrials.gov ID: NCT03849118.

[2] Positron emission tomography.

[3] Brand name subject to final regulatory approval.

[4] Kim et al. JAMA Surg. 2019.