FDA grants priority review to 89Zr-DFO-girentuximab for kidney cancer imaging

The FDA has accepted and granted priority review to the biologics license application (BLA) for the investigational PET imaging agent ⁸⁹Zr-DFO-girentuximab (TLX250-CDx; Zircaix) for clear cell renal cell carcinoma (ccRCC), Telix Pharmaceuticals announced in a news release.¹

The FDA has set the PDUFA target action date for August 27, 2025.

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

"We are delighted that the FDA has accepted this BLA as it moves us one step closer to bringing our breakthrough product to patients,” said Kevin Richardson, CEO, Precision Medicine, at Telix Pharmaceuticals, in the news 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."

The BLA was 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.²

Data from the trial, which were published in Lancet Oncology, showed that the agent had an average sensitivity of 85.5% (95% CI, 81.5-89.6) and an average specificity of 87% (95% CI, 81.0-93.1) across 3 independent readers in detecting ccRCC in patients with an indeterminate renal mass (7 cm or smaller). 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; n = 145) showed 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) with the agent. For both primary and secondary end points, the lower bounds of the 95% confidence intervals exceeded the prespecified thresholds across all readers.

Regarding safety, there were 261 adverse events (AEs) experienced among 122 patients. Of those, 13 AEs were determined to be possibly or definitely related to treatment. According to the authors, “Most adverse events were not or were unlikely to be related to [⁸⁹Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery.”

The most common adverse events of grade 3 or higher were post-procedural hemorrhage (2%), urinary retention (1%), and hypertension (1%). In total, there were 52 serious AEs reported, of which 98% occurred after surgery.

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 61 years.

All patients included in the study were given a single dose of ⁸⁹Zr-DFO-girentuximab IV (37 MBq ±10%; 10 mg girentuximab) on day 0 and underwent abdominal PET/CT imaging on day 5 (± 2 days). The co-primary outcome measures were sensitivity and specificity of ⁸⁹Zr-DFO-girentuximab in detecting ccRCC in patients with an indeterminate renal mass.

Currently, ⁸⁹Zr-DFO-girentuximab 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, ⁸⁹Zr-DFO-girentuximab would be the first commercially available targeted radiopharmaceutical imaging agent specifically for kidney cancer in the United States.

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 26, 2025. https://telixpharma.com/news-views/fda-accepts-bla-for-tlx250-cdx-zircaix-for-kidney-cancer-imaging-grants-priority-review/

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