First patient dosed with TLX250-CDx for ccRCC in Australia

The first patient has been dosed in a Special Access Scheme (SAS) in Australia for TLX250-CDx (89Zr-DFO-girentuximab, Zircaix), PET/CT imaging in patients with clear cell renal cell carcinoma (ccRCC), according to a news release from Telix, the developer of the agent.¹

Telix submitted a biologics license application to the US FDA in December 2023 for TLX250-CDx in ccRCC.

In Australia, an SAS allows physicians to apply for access to unapproved products on an individual patient basis when there are exceptional circumstances and an unmet medical need.

“It is great to now have access to this novel imaging modality, which, based on performance in clinical trials, we hope will be able to answer questions relevant to our patients. This investigational imaging tracer has demonstrated the potential to provide a clear diagnosis and treatment plan for patients with ccRCC, without the need for invasive biopsy, the standard of care, which is not always conclusive or possible,” said Andrew Weickhardt, MBBS, DMed Sc, in the news release.¹ Weickhardt is a medical oncologist at the Olivia Newton-John Cancer Wellness Centre and an associate professor of cancer medicine at La Trobe University.

The first patient was treated with TLX250-CDx at the Olivia Newton-John Cancer Wellness Centre at Austin Health in Melbourne, Australia. The center also served as one of the top recruiting sites for the phase 3 ZIRCON study (NCT03849118), which was a confirmatory study to evaluate the specificity and sensitivity of TLX25-CDx in targeting ccRCC in patients with indeterminate renal masses (IDRM) scheduled for partial nephrectomy.

In November 2022, Telix reported that the study met its primary and secondary end points by demonstrating high specificity and sensitivity of the agent in adult patients with ccRCC and an IDRM.²

In the detection of the clear cell phenotype and diagnosing the presence and spread of ccRCC, TLX250-CDx achieved a sensitivity of 86% and a specificity of 87%,both of which exceeded the pre-determined threshold of at least 70% sensitivity/specificity and thus met the trial’s primary end point.³ The sensitivity and specificity were 84% or higher across all 3 readers for each.

Additionally, the study met its secondary end point with TLX250-CDx showing a sensitivity of 85% and a specificity of 89% in the detection of ccRCC in tumors less than 4 cm (T1a disease). Among all evaluable patients, the positive predictive value was 91.7% or higher, and the negative predictive value was 73.7% or higher.

In total, the phase 3 ZIRCON trial enrolled 300 patients with ccRCC, 284 of which were included for analysis. Patients were enrolled at 36 sites across the US, Europe, and Australia. The mean age of participants was 62.

To be eligible for the ZIRCON study, patients had to have a single IDRM of 7 cm or smaller in diameter (stage cT1) as identified on CT or MRI that was suspicious for ccRCC and scheduled for surgical removal within 90 days.

Each patient included in the study received a single dose of TLX250-CDx (37 MBq ± 10%; 10 mg girentuximab) via intravenous administration on day 0 and PET/CT imaging on day 5 (± 2 days), prior to partial nephrectomy. PET/CT images were assessed by 3 blinded independent readers.The truth comparator was a histological tumor sample obtained from surgical resection.

In December 2023, a biologics license application (BLA) was submitted to the US FDA for TLX250-CDx for PET/CT imaging in ccRCC.⁴ The submission was based off findings from the phase 3 ZIRCON study. Currently, the agent has been given a rolling review process based on a breakthrough therapy designation granted in July 2020.Through the BLA submission, Telix has requested priority review for TLX250-CDx, which, if granted, would support an expedited review time.

References

1. First patient dosed in special access scheme in Australia for TLX250-CDx, Telix’s kidney cancer imaging agent. News release. Telix Pharmaceuticals. Published online April 26, 2024. Accessed April 29, 2024. https://telixpharma.com/news-views/first-patient-dosed-in-special-access-scheme-in-australia-for-tlx250-cdx-telixs-kidney-cancer-imaging-agent/

2. Telix announces positive topline results of ZIRCON phase III kidney cancer imaging study. News release. Telix Pharmaceuticals. Published online November 7, 2022. Accessed April 29, 2024. https://telixpharma.com/news-views/zircon-phase-iii-top-line-data-study-meets-primary-objectives/

3. Shuch BM, Pantuck AJ, Bernhard JC, et al. Results from phase 3 study of 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON). J Clin Oncol. 2023. doi:10.1200/JCO.2023.41.6_suppl.LBA60

4. Telix submits Biologics License Application (BLA) for TLX250-CDx (Zircaix) for imaging of kidney cancer. News release. Telix Pharmaceuticals. Published online December 19, 2023. Accessed April 29, 2024. https://telixpharma.com/news-views/telix-submits-biologics-license-application-bla-for-tlx250-cdx-zircaix-for-imaging-of-kidney-cancer/