The investigational renal (kidney) cancer imaging drug TLX250-CDx from Telix Pharmaceuticals Limited has dosed the final patient and finished enrollment in the Phase III pivotal research ZIRCON (Zirconium in Renal Cancer Oncology, NCT03849118) (89Zr-DFO-girentuximab). To present, 300 patients have received doses as part of this international study, exceeding the 252 patient enrollment goal that was set on March 8th, 2022.
TLX250-CDx is being developed as an imaging agent for use in the characterization of indeterminate renal masses that have previously been identified on computed tomography (CT) or magnetic resonance imaging (MRI) as clear cell renal cell cancer (ccRCC) or non-ccRCC. It has been given “Breakthrough Designation” by the U.S. Food and Drug Administration (FDA)1.
The extensive use of cross-sectional imaging has led to an increase in the detection of renal masses. Since current imaging cannot reliably discriminate benign or malignant lesions from renal cell carcinoma in many of these tiny renal masses, the diagnosis must be confirmed with invasive biopsy or partial nephrectomy. These processes aren’t always required and can cause problems2. Up to 80% of tiny renal tumours are thought to be cancerous3.
If the study is successful, TLX250-CDx might offer a non-invasive way to help with ccRCC diagnosis and staging as well as the detection of metastatic disease through whole body imaging. This would ultimately improve patient management by reducing the need for surgical intervention for diagnosis and directing treatment choices.
In addition to its potential use as a diagnostic and staging tool, Telix is considering the potential for TLX250-CDx to also be used as an active surveillance tool for patients not deemed surgical candidates.
“We may well be on the cusp of a paradigm shift in how we manage renal masses. The incidence of small renal masses is increasing, yet there is currently no imaging tool that can effectively diagnose or stage clear cell renal cancer. Most patients are scheduled for the operating room without a firm diagnosis and often surgery is found to be unnecessary. Should this study report positive results, it may provide the non-invasive imaging tool to aid in accurate diagnosis that patients and clinicians have been waiting for. Congratulations to Telix for completing this ambitious international trial.”
Brian M Shuch, MD, Director of the Kidney Cancer program
Renal cell carcinoma (RCC) is the deadliest of all urological cancers with a late-stage 5-year survival rate of 14%4. ccRCC is the most common sub-type and accounts for approximately 80% of all renal cell carcinoma cases5. RCC is also an increasingly frequent cancer, having more than doubled in incidence in the developed world over the last 50 years.6 Worldwide, there were more than 400,000 new cases in 2020, and >175,000 people died from their disease.7
TLX250-CDx will be available in selected countries to eligible patients under an Expanded Access Program (EAP) (also known as early access, pre-approval access or emergency use), in accordance with Telix’s Compassionate Use Policy and subject to jurisdictional regulatory requirements.8
“The completion of this trial will bring us a step closer to commercialization for this diagnostic imaging agent which may address a significant unmet need in the diagnosis and management of ccRCC. It also builds on Telix’s commitment to urologic oncology, with the potential of delivering a major new imaging indication. This milestone could have not been achieved without the support of our many collaborators including the 36 clinical sites who participated in the trial, our global manufacturing teams and the associated auxiliary team who have supported this study. Most of all we wish to thank the patients who have volunteered to participate in this study.”
Dr Colin Hayward, Telix’s Chief Medical Officer
ZIRCON is a confirmatory, prospective, open-label, multi-centre phase III study to evaluate sensitivity and specificity of 89Zr-TLX250-CDx PET/CT imaging to non-invasively detect clear cell renal cell cancer (ccRCC) in adult patients with indeterminate renal masses (IDRM), scheduled for partial or total nephrectomy. Telix expects to report the outcome from the ZIRCON study in 2H, 2022.
The investigational drug TLX250-CDx (89Zr-girentuximab) is being developed by Telix for the non-invasive detection of clear cell renal cancer in patients with “indeterminate renal masses” (IDRMs), which are typically identified based on CT or MRI imaging and are becoming a more significant medical problem as more scans are conducted and more IDRMs are discovered. Carbonic anhydrase IX (CAIX), a cell surface target that is extensively expressed in a number of human cancers including renal, lung, and oesophageal tumours, is the target of the monoclonal antibody known as girentuximab. The U.S. Food and Drug Administration (FDA) designated TLX250-CDx as a Breakthrough Therapy (BT) in July 2020, recognising the urgent clinical need to more accurately characterise ambiguous renal masses that had been classified as ccRCC or non-ccRCC on CT or MRI. , ccRCC is the most common and aggressive form of kidney cancer.
An international multicenter Phase III study called ZIRCON (Zirconium Imaging in Renal Cancer Oncology, NCT03849118) is being conducted at 34 sites in Europe, Australia, Turkey, Canada, and the United States. With the aim of comparing the sensitivity and specificity of TLX250-CDx PET imaging to the histologic “standard of truth” established from surgical resection specimens in order to detect clear cell renal cell cancer (ccRCC), ZIRCON is a prospective imaging trial in renal cancer patients undergoing kidney surgery.