Phase III ZIRCON Study of PET Imaging Agent Meets Endpoints

The pivotal Phase III ZIRCON study of Telix Pharmaceuticals Limited’s investigational renal (kidney) cancer positron emission tomography (PET) imaging agent, TLX250-CDx (89Zr-DFO-girentuximab), has met its co-primary and secondary endpoints.

The study results delivered 86% sensitivity and 87% specificity, exceeding 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. The study has also met the key secondary endpoint, achieving 85% sensitivity and 89%specificity in detecting ccRCC in tumors <4cm ("T1a" classification), currently a significant clinical challenge in the diagnosis of ccRCC.

A total of 300 patients were dosed with TLX250-CDx resulting in 284 evaluable patients. Each patient received a single dose of TLX250-CDx and a histological tumor sample from surgical resection was used as the truth comparator.

The results mean that, for the first time, urologists and urologic oncologists may have a non-invasive way to determine if small renal masses are the clear cell phenotype, the most aggressive and common form of renal malignancy. TLX250-CDx has received "Breakthrough Designation" from the FDA.

Brian Shuch, MD, Director, Kidney Cancer Program, UCLA Institute of Urologic Oncology, said, "The positive result from the study is a critical step in better diagnosing clear cell renal cancer. 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."

Gregory Jack, FRACS, General Urological Surgeon Austin Health and Olivia Newton John Cancer Centre, added, "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."

Professor Françoise Kraeber-Bodéré, MD, PhD, Nuclear Medicine Department - CHU Nantes, said, "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."

Based on these results Telix intends to file a BLA for regulatory approval with the FDA and global regulatory agencies as a positron emission tomography/computed tomography (PET/CT) imaging agent for use in the characterization of indeterminate renal masses previously identified on CT or MRI as ccRCC or non-ccRCC. Potential future utility may include active surveillance, surgical staging and treatment response assessment and the Company is actively engaged in clinical research at leading cancer centers to demonstrate the potential of these indications.

Dr Colin Hayward, Chief Medical Officer at Telix said: "The excellent sensitivity and specificity demonstrated in the ZIRCON study, validates that the CAIX target could be just as ground-breaking in ccRCC as PSMA3 and its application in PSMA-PET imaging has been for prostate cancer. It could optimise surgical intervention – particularly in the incidence of very small renal masses. These results provide confidence that TLX250-CDx is an important tool not only for initial diagnosis but potentially also for active surveillance and disease staging."