FDA requests additional data for TLX250-CDx in kidney cancer

The FDA has not accepted the biologics license application (BLA) for TLX250-CDx (⁸⁹Zr-DFO-girentuximab), an investigational imaging agent for clear cell renal cell carcinoma (ccRCC), Telix Pharmaceuticals, the developer of the agent, announced in a news release.¹

The BLA for TLX250-CDx was submitted to the FDA in June 2024.

In their review of the BLA, the FDA identified an issue in the Chemistry, Manufacturing, and Controls package. 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.”¹

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

Following this decision, Telix must resubmit the BLA with remediations in order to advance the application to full review, which the company expects to be able to complete within approximately 90 days. According to Telix, the company is still targeting a full commercial launch of TLX250-CDx in 2025.

“TLX250-CDx is a breakthrough product and, if approved, would be the first targeted imaging agent for the non-invasive detection of renal cancer,” said Christian Behrenbruch, PhD, MBA, JD, managing director and group CEO of Telix, in the news release.¹ “We have been working closely with the FDA through the BLA rolling review due to the novel nature of this product candidate and value the FDA’s constructive feedback at this early stage in the process. We expect to be able to satisfy its requirements within a minimal time frame and continue to see a clear path to product commercialization in 2025.”

The BLA for TLX250-CDx was 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.

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.²

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. BLA filing update for renal cancer imaging agent TLX250-CDx. News release. Telix Pharmaceuticals. July 31, 2024. Accessed August 5, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://company-announcements.afr.com/asx/tlx/6f71b977-4ecf-11ef-a765-2af604e39195.pdf

2. 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