Study to compare TLX250-CDx vs contrast-enhanced CT for recurrent ccRCC

The first patient has been dosed in the phase 2 CA-NINE trial (NCT06447103) comparing the diagnostic performance of TLX250-CDx (Zircaix; ⁸⁹Zr-DFO-girentuximab) PET/CT to conventional imaging (contrast-enhanced CT) for the detection of recurrent clear cell renal cell carcinoma (ccRCC) following surgery, Telix Pharmaceuticals announced in a news release.¹

The primary outcome measure for the trial is the lesion detection rate.

TLX250-CDx works by targetingthe receptor carbonic anhydrase IX (CAIX).

Telix is currently seeking approval for the radiotracer in the United States for the characterization of indeterminate renal masses suspicious of ccRCC based on data from the phase 3 ZIRCON trial (NCT03849118). Overall, data from the trial showed that TLX250-CDx 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.²

“Telix’s ZIRCON trial demonstrated the accuracy of TLX250-CDx at diagnosing localized ccRCC. However, we know that many patients die of metastatic disease, where the cancer has spread,” explained principal investigator of the CA-NINE trial, Brian M. Shuch, MD, director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the University of California, Los Angeles, in the news release.¹ “There are plenty of data showing that metastatic ccRCC also expresses the CAIX biomarker, which demonstrates potential use beyond localized ccRCC. We are on the cusp of a revolution in how we detect and manage advanced kidney cancer before and after surgery, and I'm excited to work with Telix to hopefully bring this technology to patients should it receive regulatory approval.”

In total, the prospective, single-center CA-NINE trial plans to enroll 91 patients with intermediate- to high-risk ccRCC following surgery. Patients included in the study will receive TLX250-CDx IV over 3 minutes on day 0 and then undergo whole-body PET/CT and diagnostic contrast-enhanced CT scan on day 7.³

The primary outcome measure for the trial is the lesion detection rate. Secondary outcome measures include the incidence of adverse events, positive predictive value, recurrence-free survival, and the change in management and perceived clinical utility based on the unblinded read of PET/CT.

“We are pleased that a first patient has been imaged in the CA-NINE trial, which supports potential label expansion for TLX250-CDx into recurrent, metastatic disease,” said David N. Cade, Chief Medical Officer at Telix, in the news release.¹ “We would like to thank Professor Shuch and Associate Professor Calais at UCLA for their commitment to addressing unmet medical need in kidney cancer, as well as the patients who will contribute to this important trial.”

Primary completion of the CA-NINE trial is anticipated for December 2029.

Additional information on TLX250-CDx

Telix initially submitted a biologics license application (BLA) for TLX250-CDx in June 2024 seeking FDA approval of the agent 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.4 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 a news release, “Telix can confirm that despite this concern raised by the FDA, all Process Performance Qualification batches submitted as part of the BLA application passed the sterility requirements of product release.”⁴

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 to advance the application to full review. At the time of this announcement in July 2024, the company stated that they expected 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, pending FDA approval.

References

1. First patient dosed in phase II ‘CA-NINE’ trial of TLX250-CDx for detection of recurrent kidney cancer after surgery. News release. Telix Pharmaceuticals. October 3, 2024. Accessed October 4, 2024. https://www.globenewswire.com/en/news-release/2024/10/03/2957584/0/en/First-Patient-Dosed-in-Phase-II-CA-NINE-Trial-of-TLX250-CDx-for-Detection-of-Recurrent-Kidney-Cancer-After-Surgery.html

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. Published online September 10, 2024. Accessed October 4, 2024. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00402-9/fulltext

3. An investigational scan (89Zr-DFO-GmAb PET/​CT) compared to contrast-enhanced CT for the detection of recurrent clear cell renal cell cancer after surgery comparing carbonic anhydrase IX (CAIX) PET CT to conventional PET CT for post-op staging in kidney cancer. ClinicalTrials.gov. Last updated August 21, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT06447103

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