Approval sought for TLX250-CDx in clear cell renal cell carcinoma

Telix Pharmaceuticals has completed the submission of a Biologics License Application (BLA) to the FDA to support approval of their radiodiagnostic PET agent, TLX250-CDx (Zircaix; 89Zr-DFO-girentuximab), for imaging of clear cell renal cell carcinoma (ccRCC), the company announced in a news release.¹

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.

The BLA submission was first initiated in December 2023, with timelines pre-agreed with the FDA. In addition to the BLA, Telix has also requested priority review for TLX250-CDx, which would expedite the review time for the agent, if granted. Currently, the agent has been awarded a rolling review process based on a breakthrough therapy designation granted in July 2020.²

TLX250-CDx is the latest product in Telix’s imaging portfolio. The company’s lead prostate cancer imaging product, TLX591-CDx (Illuccix), a radiopharmaceutical cold kit for the preparation of 68Ga-PSMA-11 injection, was granted FDA approval in December 2021.³

"Completing the BLA submission for TLX250-CDx represents a significant milestone for Telix as we bring our Breakthrough investigational kidney cancer imaging agent closer to market as a non-invasive diagnostic for patients,” said James Stonecypher, chief development officer at Telix, in the news release.¹ “We believe TLX250-CDx is a natural follow-on product to Illuccix as it is targeted at the same clinical stakeholders, the urologist and urologic oncologist, and leverages the proven commercial and distribution infrastructure developed through the launch of Illuccix."

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.⁴

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; 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 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 primary outcomes for analysis were sensitivity and specificity 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 completes TLX250-CDx (Zircaix®) BLA submission for kidney cancer imaging. News release. Telix Pharmaceuticals. June 2, 2024. Accessed June 10, 2024. https://telixpharma.com/news-views/telix-completes-tlx250-cdx-zircaix-bla-submission-for-kidney-cancer-imaging/

2. Telix granted FDA Breakthrough Therapy Designation for renal cancer imaging product. News release. Telix Pharmaceuticals. July 1, 2020. Accessed June 10, 2024. https://telixpharma.com/news-views/telix-granted-fda-breakthrough-therapy-designation-for-renal-cancer-imaging-product/

3. FDA Approves Telix’s Prostate Cancer Imaging Product, Illuccix. News release. Telix Pharmaceuticals. December 20, 2021. Accessed June 10, 2024. https://telixpharma.com/news-views/fda-approves-telixs-prostate-cancer-imaging-product-illuccix/

4. 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