Study launches of novel radiopharmaceutical TLX250 in kidney cancer

The first patient has been dosed in the phase 2 STARLITE 2 trial, which is exploring the combination of the novel radiopharmaceutical TLX250 (¹⁷⁷Lu-DOTA-girentuximab) and the immunotherapy nivolumab (Opdivo) in patients with advanced renal cell carcinoma (RCC).¹

TLX250 targets the protein carbonic anhydrase IX (CA9). Previous research identified high expression of CA9 among patients with cancer who did not have a strong response to immunotherapy. The hypothesis of STARLITE 2 (NCT05239533) is that by targeting CA9, TLX250 will enable the patient to overcome this is immune resistance and respond to nivolumab.

The targeted enrollment for the trial is 30 patients with clear cell RCC who have progressed after receiving prior immunotherapy. The investigational companion imaging agent TLX250-CDx (⁸⁹Zr-DFO-girentuximab) will be used in the study to measure CA9 expression.

Patients will receive combination therapy with nivolumab plus low doses of targeted radiation with TLX250. The primary end point of the trial is the efficacy of the exploratory combination as measured by objective response rate (RECIST v1.1 criteria).

The initial patient was treated at Memorial Sloan Kettering Cancer Center in New York City by a team led by Darren R. Feldman, MD.

"The integration of precision nuclear medicine and medical oncology is underway and Telix is at the forefront of this movement to develop personalized products and patient-friendly regimens. We wish to express our gratitude to Dr Feldman and his clinical team, as well as the patients who will contribute to this ground-breaking study," Colin Hayward, MD, chief medical officer at Telix Pharmaceuticals, the developer of TLX250 and TLX250-CDx, stated in a press release.

Phase 3 ZIRCON trial of TLX250-CDx

The novel PET imaging agent TLX250-CDx is itself being explored in the phase 3 ZIRCON trial (NCT03849118).² The goal of the ZIRCON trial is to establish the efficacy of TLX250-CDx as a noninvasive tool to identify clear cell RCC in patients with indeterminate renal masses. The primary outcome measures are sensitivity and specificity.

The FDA granted a Breakthrough Therapy Designation to TLX250-CDx in July 2020 for the diagnosis and staging of indeterminate renal masses.³ The designation is intended to expedite the development and regulatory review of the imaging radiopharmaceutical in this setting.

Overall, the prospective, international, open-label, single-group assignment, phase 3 ZIRCON trial is exploring TLX250-CDx in patients with indeterminate renal masses scheduled for partial or total nephrectomy. The indeterminant renal mass must be a maximum of 7 cm in largest diameter (tumor stage cT1) and the nephrectomy must occur within 90 days of the administration of TLX250-CDx.⁴ The efficacy of TLX250-CDx will be determined through a comparison with histologic results with surgical resection as the “standard of truth.”

The study is being conducted at 36 locations in Europe, Australia, Turkey, Canada, and the United States. The targeted enrollment is 252 patients.

References

1. First Patient Dosed in Phase II Renal Cancer Theranostics. Published online May 4, 2022. Accessed May 5, 2022. https://prn.to/3shbqn7

2. First U.S. Patients Dosed in Phase III ZIRCON Trial of Renal Cancer Imaging Product. Published online January 25, 2021. Accessed January 25, 2021. https://bit.ly/39gwHnK.

2. Telix Granted FDA Breakthrough Therapy Designation for Renal Cancer Imaging Product. Published online July 1, 2020. Accessed January 25, 2021. https://bit.ly/39hkIpT.

3. NIH US National Library of Medicine ClinicalTrials.gov. 89Zr-TLX250 for PET/CT Imaging of ccRCC- ZIRCON Study (89ZR-TLX250). Last updated October 19, 2020. Accessed January 25, 2021. https://clinicaltrials.gov/ct2/show/NCT03849118