FDA Grants Priority Review to TLX250-CDx in Kidney Cancer

US FDA

• The FDA has accepted and granted priority review to the biologics license application (BLA) of TLX250-CDx (Zircaix, 89Zr-DFO-girentuximab) for the treatment of clear cell renal cell carcinoma (ccRCC).
• A Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025, has been set by the FDA.
• If approved, TLX250-CDx will become the first targeted radiopharmaceutical imaging agent available for patients with kidney cancer in the US.

The FDA accepted and granted priority review to the BLA of TLX250-CDx for the potential treatment of patients with clear cell renal cell carcinoma (ccRCC).¹ With this, the FDA has set a PDUFA target action date for August 27, 2025.

Findings from the phase 3 ZIRCON trial (NCT03849118) support this regulatory decision as all of the co-primary and secondary end points of the study were met with the agent demonstrating high specificity and sensitivity for PET/CT imaging of ccRCC.² Data from the trial were published in Lancet Oncology, showing that the agent met a sensitivity of 86%, a specificity of 87%, and a positive predictive value of 93% for ccRCC. This included lesions that were small and difficult to detect.

In a secondary analysis focusing on patients with small masses (≤4 cm; cT1a; n = 145), the agent demonstrated an average sensitivity of 83.5% (95% CI, 74.6%-89.8%) and an average specificity of 90.7% (95% CI, 80.1%-96.0%). For both primary and secondary end points, the lower bounds of the 95% confidence intervals surpassed the prespecified thresholds across all readers.

"We are delighted that the FDA has accepted this BLA as it moves us one step closer to bringing our breakthrough product to patients,” Kevin Richardson, chief executive officer, Precision Medicine, at Telix Pharmaceuticals, said in the press release.¹ “We are aiming to revolutionize the management of kidney cancer, just as PSMA-PET/CT scanning has changed the management of prostate cancer. By providing a more definitive clinical diagnosis for renal masses, we believe that Zircaix will help physicians make more timely and confident patient management decisions and more quickly provide patients with a clear understanding of their disease and treatment options. Building further on Telix's successful urology franchise, we are preparing to bring this powerful precision medicine product to market in 2025."

3D rendering of kidney cancer with organs and tumors: © Matthieu - stock.adobe.com

Safety findings revealed there to be 261 adverse events (AEs) among the 122 patients enrolled.² Thirteen of the AEs were determined to be possibly or definitely related to treatment, and the most common AEs deemed grade 3 or higher included post-procedural hemorrhage (2%), urinary retention (1%), and hypertension (1%). Further, 52 serious AEs were reported, 98% of which occurred after surgery.

TLX250-CDx is currently available for patients outside of clinical trials through an expanded access program in the US, named patient programs in Europe, and a special access scheme in Australia, specifically for those without comparable or satisfactory diagnostic alternatives.¹

If approved, TLX250-CDx would become the first commercially available targeted radiopharmaceutical imaging agent in the US designed specifically for kidney cancer.

About the ZIRCON Trial

The confirmatory, prospective, open-label, multicenter, phase 3 ZIRCON included 371 patients who were screened and 332 who were enrolled. A total of 300 patients made up the safety analysis set, with 284 in the full analysis set.³

The sensitivity and specificity of 89Zr-TLX250 PET/CT imaging to non-invasively detect ccRCC in adult patients with indeterminate renal masses, scheduled for partial or total nephrectomy was evaluated in the trial.

The mean age of patients in the trial was 61 years. Once enrolled, patients received the agent at a dose of 37 MBq (1 mCi)/10 mg on day 0.

The coprimary end points of the trial included sensitivity and specificity of the agent vs central histology, or surgical resection, in the detection of ccRCC. Key secondary end points evaluated were sensitivity and specificity of TLX250-CDx in a cT1a (≤4 cm) subgroup.

REFERENCES:

1. FDA accepts BLA for TLX250-CDx (Zircaix) for kidney cancer imaging, grants priority review. News release. Telix Pharmaceuticals. February 25, 2025. Accessed February 28, 2025. https://tinyurl.com/2vfpy35n

2. Shuch B, Pantuck AJ, Bernhard JC, et al. [89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024;25(10):1277-1287. doi:10.1016/S1470-2045(24)00402-9

3. 89Zr-TLX250 for PET/CT imaging of ccRCC- ZIRCON study (89ZR-TLX250). ClinicalTrials.gov. Updated May 17, 2024. Accessed February 28, 2025. https://www.clinicaltrials.gov/study/NCT03849118