(UroToday.com) The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting was host to a kidney and bladder cancers poster session. Dr. David Cade presented LUTEON, an ongoing phase III trial to assess the safety and efficacy of 177Lu-girentuximab in advanced, relapsed, or recurrent clear cell renal cell carcinoma (ccRCC).
Despite significant therapeutic advances in metastatic ccRCC, there remains an unmet need for treatments capable of providing durable disease control while preserving quality of life. Carbonic anhydrase IX (CAIX) is an attractive therapeutic target in ccRCC, with expression observed in more than 95% of clear cell RCC tumors and limited expression in normal tissues. Girentuximab is a monoclonal antibody directed against CAIX, and radiolabeling girentuximab with the beta-emitting radionuclide lutetium-177 enables targeted radiation delivery to CAIX-expressing tumor cells. Early phase I/II studies of 177Lu-girentuximab have demonstrated encouraging safety, tolerability, and antitumor activity in metastatic ccRCC, providing the rationale for further development in a phase III setting.
LUTEON is a two-part, randomized, open-label, multicenter study designed to first identify the optimal activity and treatment schedule of 177Lu-girentuximab and subsequently compare the selected regimen with an approved standard-of-care (SOC) monotherapy.
Eligible patients must be:
- ≥18 years of age
- Have histologically or cytologically confirmed locally advanced or metastatic relapsed/recurrent ccRCC
- Have received 2–3 prior lines of systemic therapy for advanced disease, including both a PD-1/PD-L1 inhibitor and a VEGF/VEGFR-targeted agent
- Demonstrate CAIX-positive disease on screening 89Zr-girentuximab PET imaging
In Part 1, patients are randomized 1:1 (up to 20 patients per arm) to one of two dosing schedules:
- Three intravenous infusions of 1887 MBq 177Lu-girentuximab administered every 8 weeks
- Six intravenous infusions of 1258 MBq 177Lu-girentuximab administered every 4 weeks
Treatment-related toxicities are managed using predefined dose-modification and supportive-care strategies. Based on the safety and activity observed in Part 1, an optimal regimen will be selected for evaluation in Part 2.
In Part 2, patients will be randomized 1:1 to receive either:
- 177Lu-girentuximab at the optimal regimen identified in Part 1
- An approved standard-of-care monotherapy comparator
Patients undergo an end-of-treatment visit approximately 3 ± 1 weeks following the final infusion or within 30 days of treatment discontinuation. After treatment completion, efficacy assessments are performed every 8 ± 2 weeks for the first 6 months and include tumor evaluations according to RECIST v1.1 using contrast-enhanced CT and/or MRI of the chest, abdomen, and pelvis. In Part 2, patients continue long-term follow-up every 12 ± 2 weeks for up to 24 months after treatment completion, or until disease progression, death, or initiation of subsequent systemic therapy.
The primary endpoints of Part 1 focus on safety and tolerability and include:
- Incidence and severity of treatment-emergent adverse events (TEAEs)
- Treatment discontinuation due to TEAEs
- Dose delays resulting from TEAEs
The primary endpoint of Part 2 is progression-free survival (PFS), defined as the time from randomization to RECIST v1.1 disease progression or death from any cause.
LUTEON is the first phase III study of CAIX-targeted radioligand therapy in advanced ccRCC and incorporates molecular selection using 89Zr-girentuximab PET imaging to identify patients with CAIX-positive disease. By combining a highly tumor-specific target with targeted radionuclide delivery, the study seeks to determine whether 177Lu-girentuximab can provide meaningful clinical benefit in patients with heavily pretreated advanced ccRCC. If successful, LUTEON could establish a novel biomarker-selected radioligand treatment strategy for renal cell carcinoma.
Presented by: David N. Cade, Group Chief Medical Officer, Telix Pharmaceuticals
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center, Tucson, AZ – @rksayyid on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026