FDA Accepts Biologics License Application for Novel PET Imaging Agent for Renal Cell Carcinoma

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Telix Pharmaceuticals has filed a biologics license application (BLA) to the FDA for the novel positron emission tomography (PET) imaging agent 89Zr-DFO-girentuximab (TLX250-CDx; Zircaix) for clear cell renal cell carcinoma (ccRCC).¹ The BLA submission was based on data from the Phase III ZIRCON trial (NCT03849118), which showed girentuximab was more effective than traditional PET/CT imaging in identifying malignant RCC lesions.²

“The ZIRCON study demonstrated the superior sensitivity and specificity of this advanced diagnostic imaging agent, which, if approved, will be the first and only agent available to target carbonic anhydrase IX, a highly relevant target in kidney cancer,” said Brian Shuch, MD, associate professor, director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at UCLA Institute of Urologic Oncology, in a press release.¹ “This delivers on a major unmet need to provide confidence in the diagnosis of ccRCC, the most aggressive and common form of kidney cancer.”

Preliminary results from the ZIRCON trial were presented during the 2023 Genitourinary Cancers Symposium.

The confirmatory, prospective, open-label, multi-center trial was designed to analyze the sensitivity and specificity of girentuximab compared with PET/CT imaging for use as a non-invasive method to detect ccRCC in adults with indeterminate renal masses.³ Investigators enrolled patients with a single indeterminate renal mass 7 cm or smaller in diameter (cT1) on CT or MRI for suspected ccRCC that was set for excision with partial or total nephrectomy.^2,3

The trial’s co-primary endpoints were the sensitivity and specificity of girentuximab compared with central histology or surgical resection for the detection of ccRCC. Secondary endpoints included the sensitivity and specificity of girentuximab in a cT1a (≤4 cm) subgroup.²

Trial data show that sensitivity and specificity rates with girentuximab in the full analysis set were 85.5% (95% CI, 79.8%-89.8%) and 87% (95% CI, 78.8%-92.3%), respectively; positive predictive value was 93% (95% CI, 88%-96%); negative predictive value was 75% (95% CI, 66%-82%); and the accuracy rate was 86% (95% CI, 81.5%-89.6%).

“This is a major milestone and achievement for Telix, which paves the way for a commercial availability for patients in the US in 2024, subject to regulatory review and approval,” Dr. Christian Behrenbruch, PhD, managing director and chief executive officer of Telix Group CEO, stated in a news release.¹

The FDA previously granted breakthrough therapy designation to girentuximab in July 2020.4 The BLA submission seeks for the FDA to grant priority review status to girentuximab.¹

“If approved by the FDA, TLX250-CDx will be the first targeted radiopharmaceutical imaging agent for kidney cancer to be commercially available to patients in the US,” said James Stonecypher, chief development officer at Telix, press release. “The collaborative approach shown by the FDA under the breakthrough therapy designation has been highly valuable as we work to bring this novel, non-invasive, first-in-class 89-zirconium-labeled monoclonal antibody-based imaging agent to market.”¹

References

1. Telix submits biologics license application (BLA) for TLX250-CDx (Zircaix™) for imaging of kidney cancer. News release. Telix. December 19, 2023. Accessed January 4, 2024. https://telixpharma.com/news-views/telix-submits-biologics-license-application-bla-for-tlx250-cdx-zircaix-for-imaging-of-kidney-cancer/#:~:text=Telix%20today%20announces%20that%20it,renal%20cell%20carcinoma%20(ccRCC)

2. Shuch BM, Pantuck AJ, Bernhard J-C, et al. Results from phase 3 study of 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON). J Clin Oncol. 2023;41(suppl 6):LBA602. doi:10.1200/JCO.2023.41.6_suppl.LBA602

3. 89Zr-TLX250 for PET/CT imaging of ccRCC-ZIRCON study (89ZR-TLX250). ClinicalTrials.gov. Updated April 14, 2023. Accessed January 4, 2024. https://clinicaltrials.gov/study/NCT03849118

4. Telix granted FDA breakthrough therapy designation for renal cancer imaging product. News release. Telix. July 1, 2020. Accessed January 4, 2024. https://telixpharma.com/news-views/telix-granted-fda-breakthrough-therapy-designation-for-renal-cancer-imaging-product/