TLX250-CDx data published in Lancet Oncology as company seeks FDA approval

Data from the phase 3 ZIRCON trial (NCT03849118) evaluating TLX250-CDx (Zircaix, 89Zr-girentuximab) in patients with an indeterminate renal mass suspicious of clear cell renal cell carcinoma (ccRCC) have been published in The Lancet Oncology¹ as the company looks to resubmit a biologics license application (BLA) for the imaging agent.

Telix must resubmit the BLA for TLX250-CDx with remediations in order to advance the application to full review.

Overall, the trial reported high accuracy of TLX250-CDx in detecting and characterizing ccRCC in patients with indeterminate renal masses.

"Until now, assessing whether renal masses are cancerous has been difficult and often involves invasive surgery or percutaneous biopsy. This is because standard imaging technology––either a CT or MRI scan––cannot reliably differentiate between benign or malignant renal lesions or provide information about disease biology,” explained ZIRCON principal investigator Brian Shuch, MD, in a news release from Telix.² Shuch is the director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the University of California, Los Angeles.

Specifically, data from the phase 3 ZIRCON trial 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. 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 smaller; 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. The most common AEs of grade 3 or higher were post-procedural hemorrhage (2%; 6 of 261), urinary retention (1%; 3 of 261), and hypertension (1%; 3 of 261). Further, 52 serious adverse events were reported in 25 of 300 (8%) patients. Of these, 51 (98%) occurred after surgery. There were no treatment-related deaths.

In total, the prospective, open-label, multicenter ZIRCON study enrolled 300 adult patients with an indeterminate renal mass (7 cm or smaller; cT1) suspicious for ccRCC who were scheduled for partial or total nephrectomy. Of those, 284 evaluable patients were included in the primary analysis. The average age of patients in the trial was 61 years.

All participants 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). Patients underwent nephrectomy no later than 90 days following administration of TLX250-CDx.

The co-primary outcome measures were sensitivity and specificity of TLX250-CDx in detecting ccRCC in patients with an indeterminate renal mass. The study’s key secondary end points were the sensitivity and specificity of TLX250-CDx in detecting ccRCC in patients with a CT1a indeterminate renal mass (4 cm or smaller).

Shuch added in the news release, "The challenges and uncertainty in diagnosing ccRCC underscore a critical unmet need for a new, non-invasive technique that accurately detects and differentiates ccRCC from other renal masses in patients, to inform clinical decision making. The ZIRCON trial has shown that TLX250-CDx is a breakthrough technology that can address this need."²

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 PET agent specifically for kidney cancer in the United States.

Additional information on TLX25-CDx

Telix originally submitted a BLA in June 2024 seeking FDA approval of TLX250-CDx for the characterization of indeterminate renal masses suspicious of ccRCC. The FDA responded with a complete response letter to the company, citing 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.”³

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 for TLX250-CDx with remediations in order to advance the application to full review. At the time of this report in July 2024, the company stated that they expect to be able to complete remediations within approximately 90 days. According to Telix, the company is still targeting a full commercial launch of TLX250-CDx in 2025.

References

1. 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. Published online September 10, 2024. Accessed September 11, 2024. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00402-9/fulltext

2. 'Highly accurate': Telix's phase III ZIRCON trial for kidney cancer imaging published in The Lancet Oncology. News release. Telix Pharmaceuticals Limited. September 10, 2024. Accessed September 11, 2024. https://www.prnewswire.com/news-releases/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology-302244423.html

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