Telix Pharmaceuticals Limited has announced the dosing of the first patient in its Phase II CA-NINE trial, evaluating TLX250-CDx (89Zr-girentuximab) for the detection of recurrent clear cell renal cell carcinoma (ccRCC) following surgery. The trial, led by Professor Brian Shuch at UCLA, aims to compare the diagnostic performance of TLX250-CDx PET/CT imaging to conventional contrast-enhanced CT in 91 patients with intermediate-to-high risk ccRCC. This study could pave the way for label expansion of TLX250-CDx, offering a more accurate method for identifying recurrent and metastatic ccRCC.
CA-NINE Trial Design and Objectives
The CA-NINE trial (NCT06447103) is a prospective, single-center study designed to assess the lesion detection rate of TLX250-CDx PET/CT compared to contrast-enhanced CT. Secondary outcome measures include the incidence of adverse events, positive predictive value, recurrence-free survival, and changes in clinical management based on PET/CT findings. Patients will receive TLX250-CDx intravenously, followed by PET/CT and contrast-enhanced CT scans.
TLX250-CDx: Targeting CAIX in ccRCC
TLX250-CDx is an investigational PET agent that targets carbonic anhydrase IX (CAIX), a biomarker highly expressed in ccRCC. This targeted approach allows for enhanced detection of ccRCC, potentially improving the characterization of indeterminate renal masses and identifying sites of recurrent disease. Professor Shuch emphasized that metastatic ccRCC also expresses the CAIX biomarker, suggesting potential utility beyond localized ccRCC.
Prior Clinical Evidence: ZIRCON Trial
Telix's pivotal Phase III ZIRCON trial (NCT03849118) demonstrated the accuracy of TLX250-CDx in diagnosing localized ccRCC. The trial, involving 300 patients, showed 86% sensitivity and 87% specificity, with a 93% positive-predictive value for ccRCC across three independent readers, as published in Lancet Oncology. These results indicate that TLX250-CDx can reliably detect the clear cell phenotype, providing a non-invasive method for diagnosing ccRCC.
Clinical Significance and Future Implications
Early and accurate detection of recurrent ccRCC is critical for improving patient outcomes. Associate Professor Jeremie Calais noted the limitations of conventional imaging in staging patients and expressed hope that TLX250-CDx will improve patient outcomes by identifying recurrent ccRCC outside of the kidney. Dr. David N. Cade, Chief Medical Officer at Telix, highlighted that the CA-NINE trial supports potential label expansion for TLX250-CDx into recurrent, metastatic disease, addressing a significant unmet medical need in kidney cancer.
Regulatory Status and Access Programs
Telix is seeking approval for TLX250-CDx in the United States for characterizing indeterminate renal masses suspicious of ccRCC. While the FDA issued a complete response letter citing manufacturing concerns, Telix is working to resubmit the BLA. In the meantime, Telix continues to offer access to TLX250-CDx through expanded access programs in the U.S., named patient programs in Europe, and special access schemes in Australia.
