TLX250-CDx BLA resubmitted to FDA for kidney cancer

Telix Pharmaceuticals has resubmitted a biologics license application (BLA) to the FDA to support approval of TLX250-CDx (Zircaiz; ⁸⁹Zr-DFO-girentuximab) for imaging in clear cell renal cell carcinoma (ccRCC), the company announced in a news release.¹

The BLA submission is supported by findings from the phase 3 ZIRCON trial.

“We are pleased to be progressing the BLA for TLX250-CDx, which has been granted Breakthrough designation, and may therefore be eligible for priority review,” said Kevin Richardson, CEO of Precision Medicine at Telix, in the news release.¹ “Telix continues to target a full US commercial launch in 2025 addressing a major unmet medical need for patients with suspected ccRCC.”

According to the company, a PDUFA date is expected to be issued following the 60-day administrative review of the application.

The BLA was initially submitted to the FDA in June 2024. In addition to the BLA, Telix also requested priority review for TLX250-CDx, which would expedite the review time for the agent, if granted. The agent was previously awarded a rolling review process based on a breakthrough therapy designation granted in July 2020.

However, in their review of the initial application, the agency issued a complete response letter, citing an issue in the Chemistry, Manufacturing, and Controls package.² Specifically, they noted concerns in the demonstration of adequate sterility assurance during dispensing of TLX250-CDx in the radiopharmacy production environment.

On this, the company commented in the news release, “Telix can confirm that despite this concern raised by the FDA, all Process Performance Qualification (PPQ) batches submitted as part of the BLA application passed the sterility requirements of product release.”²

The FDA did not identify any issues regarding the clinical and nonclinical safety and efficacy data for the agent.

Data on TLX250-CDx

The BLA submission for TLX250-CDx is supported by findings from the phase 3 ZIRCON trial (NCT03849118), which met all co-primary and secondary end points by demonstrating high specificity and sensitivity of the agent for PET/CT imaging of ccRCC.³

Overall, data from the trial showed that the agent had an average sensitivity of 86% and an average specificity of 87% across 3 independent readers in detecting ccRCC in patients with an indeterminate renal mass. Further, the agent demonstrated a positive predictive value of 93% for ccRCC, including in small and difficult to detect lesions.

A secondary outcome analysis of patients with small masses (defined as 4 cm or less; cT1a) showed an average sensitivity of 85.5% and an average specificity of 89.5% with the agent. For both primary and secondary end points, the lower bounds of the 95% confidence intervals exceeded 75% across all readers.

Regarding safety, there were 263 adverse events (AEs) experienced among 124 patients. Of those, 2 AEs of mild intensity were determined to be related to treatment.

In total, the open-label, multi-center ZIRCON study enrolled 300 adult patients with ccRCC who were scheduled for partial or total nephrectomy. Of those, 284 evaluable patients were included in the primary analysis. The mean age of patients in the trial was 62.

All patients included in the study were given a single dose of TLX250-CDx IV (10 mg girentuximab) on day 0 and underwent PET/CT imaging on day 5 (± 2 days). The co-primary outcome measures were sensitivity and specificity of TLX250-CDx in detecting ccRCC in patients with an indeterminate renal mass.

Currently, TLX250-CDx is available through an expanded access program in the United States, named patient programs in Europe, and a special access scheme in Australia for patients outside of clinical trials for whom there is no comparable or satisfactory alternatives. If approved, TLX250-CDx would be the first commercially available targeted radiopharmaceutical imaging agent specifically for kidney cancer in the United States.

References

1. Telix files TLX250-CDx (Zircaix) BLA for kidney cancer imaging. News release. Telix Pharmaceuticals Limited. December 30, 2024. Accessed January 2, 2025. https://telixpharma.com/news-views/telix-files-tlx250-cdx-zircaix-bla-for-kidney-cancer-imaging/

2. BLA filing update for renal cancer imaging agent TLX250-CDx. News release. Telix Pharmaceuticals. July 31, 2024. Accessed January 2, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://company-announcements.afr.com/asx/tlx/6f71b977-4ecf-11ef-a765-2af604e39195.pdf

3. Shuch BM, Pantuck AJ, Bernhard JC, et al. 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma – results from a phase 3 ZIRCON study. Presented at: 2023 ASCO Genitourinary Cancers Symposium. San Francisco, California. LBA602. https://ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.LBA602