The phase 3 ZIRCON trial (NCT03849118) exploring the novel PET imaging radiopharmaceutical TLX250-CDx (89Zr-DFO-girentuximab) in clear cell renal cell carcinoma (ccRCC) has met its co-primary endpoints.1
Telix Pharmaceuticals, the developer of TLX250-CDx, reported in a news release that the primary study end point was met with the imaging agent delivering 86% sensitivity and 87% specificity. These figures, according to Telix, “exceed[ed] the pre-determined threshold required to demonstrate the ability of TLX250-CDx to reliably detect the clear cell phenotype and provide a non-invasive method of diagnosing the presence and spread of ccRCC.”
Gregory Jack, FRACS, general urological surgeon, Austin Health and Olivia Newton John Cancer Centre, Melbourne, Australia, stated in the news release, "Kidney cancer is a diagnostic dilemma for the majority of our patients. Without biopsy or surgery, we can't currently give them the information they need. Based on this result from the ZIRCON Phase III study, TLX250-CDx may help us to be more accurate in who we treat, whilst also providing reassurance for those patients who don't need treatment."
Telix also reported that the key secondary end point of detection proficiency in patients with ccRCC and tumors <4cm (T1a classification) was achieved with TLX250-CDx achieving 85% sensitivity and 89% specificity in this patient population.
"Having an imaging product like TLX250-CDx will be so important in managing the continued increase in incidence of small renal masses and reducing the need for unnecessary invasive surgery for lesions that in the prior era were often found to be benign at the time of surgery," Brian Shuch, MD, director, Kidney Cancer Program, UCLA Institute of Urologic Oncology, stated in the news release.
The prospective, international, open-label, single-group assignment, phase 3 ZIRCON trial is exploring TLX250-CDx in patients with indeterminate renal masses scheduled for partial or total nephrectomy. The indeterminant renal mass must be a maximum of 7 cm in largest diameter (tumor stage cT1) and the nephrectomy must occur within 90 days of the administration of TLX250-CDx.2 The efficacy of TLX250-CDx is being determined through a comparison with histologic results with surgical resection as the “standard of truth.”
The study is being conducted at 36 locations in Europe, Australia, Turkey, Canada, and the United States. There have been 300 patients dosed with TLX250-CDx and the efficacy population for this analysis consisted of 284 patients. According to Telix, “each patient received a single dose of TLX250-CDx and a histological tumor sample from surgical resection was used as the truth comparator.”
TLX250-CDx uses the anti-CAIX monoclonal antibody girentuximab to target the cell-surface antigen CAIX. The antigen is found on over 90% of ccRCC cells, but is not found in normal kidney cells. CAIX is also expressed in metastatic disease, and Telix suggests this might enhance the accuracy of staging patients with ccRCC.
"Results from the Phase III ZIRCON study of TLX250-CDx should represent a major milestone in the management of small renal lesions and the diagnosis of clear cell renal cell carcinoma. There is so much potential in optimal targeting of CAIX, paving the way for better staging of this neoplasia and a theranostic approach," Françoise Kraeber-Bodéré, MD, PhD, head of the Nuclear Medicine Department – CHU de Nantes, Nantes, France, stated in the news release.
The FDA granted a Breakthrough Therapy Designation to TLX250-CDx in July 2020 for the diagnosis and staging of indeterminate renal masses.3 Based on the positive topline results from the ZIRCON trial, Telix plans to explore regulatory filings with the FDA and other regulatory agencies worldwide.
1. Telix Announces Positive Topline Results of ZIRCON Phase III Kidney Cancer Imaging Study Published online and accessed November 6, 2022. https://prn.to/3UmLSAR
2. NIH US National Library of Medicine ClinicalTrials.gov. 89Zr-TLX250 for PET/CT Imaging of ccRCC- ZIRCON Study (89ZR-TLX250). Last updated October 19, 2020. Accessed January 25, 2021. https://clinicaltrials.gov/ct2/show/NCT03849118
3. Telix Granted FDA Breakthrough Therapy Designation for Renal Cancer Imaging Product. Published online July 1, 2020. Accessed January 25, 2021. https://bit.ly/39hkIpT.