BLA Submitted to FDA for PET Imaging Agent TLX250-CDx in RCC

FDA

A biologics license application (BLA) seeking the approval of the investigational positron emission tomography (PET) imaging agent 89Zr-DFO-girentuximab (TLX250-CDx; Zircaix) in clear cell renal cell carcinoma (ccRCC) has been submitted to the FDA.¹

The submission is based on data from the global phase 3 ZIRCON trial (NCT03849118) in which the investigational imaging agent proved more effective than traditional PET/CT imaging in identifying malignant RCC lesions.²

Preliminary results, which were presented during the 2023 Genitourinary Cancers Symposium, indicated that the sensitivity and specificity rates with 89Zr-DFO-girentuximab in the full analysis set were 85.5% (95% CI, 79.8%-89.8%) and 87% (95% CI, 78.8%-92.3%), respectively. The positive predictive value was 93% (95% CI, 88%-96%), the negative predictive value was 75% (95% CI, 66%-82%), and the accuracy rate was 86% (95% CI, 81.5%-89.6%).

“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. This delivers on a major unmet need to provide confidence in the diagnosis of ccRCC, the most aggressive and common form of kidney cancer,” 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 said.¹

In July 2020, the FDA granted breakthrough therapy designation to the imaging agent.³ Telix has also requested that the imaging agent receive priority review status with the BLA submission.¹

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

ZIRCON is a confirmatory, prospective, open-label, multi-center trial designed to compare the sensitivity and specificity of 89Zr-DFO-girentuximab and PET/CT imaging when used as ato non-invasive method forlydetecting ccRCC in adult patients with indeterminate renal masses.⁴

The trial enrolled patients with a single indeterminate renal mass 7 cm or smaller in diameter (cT1) on CT or MRI that was suspicious for ccRCC and scheduled for surgical removal with partial or total nephrectomy.^2,4

The co-primary end points of the trial were the sensitivity and specificity of 89Zr-DFO-girentuximab vs central histology, or surgical resection, in the detection of ccRCC. Secondary end points included the sensitivity and specificity of 89Zr-DFO-girentuximab in a cT1a (≤4 cm) subgroup.²

“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 U.S.. 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,” James Stonecypher, chief development officer at Telix, said.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. 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/ 
4. 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