Phase 3 study to assess the safety and efficacy of ¹⁷⁷ Lu-girentuximab in advanced, relapsed, or recurrent ccRCC (LUTEON).

Abstract

TPS4631 Background: A high unmet need remains for treatments that provide durable disease control while preserving quality of life in patients with advanced clear-cell renal cell carcinoma (ccRCC). Girentuximab is a monoclonal antibody targeting carbonic anhydrase IX (CAIX), which is expressed on >95% of ccRCC cells with limited expression in healthy tissues. Radiolabeling girentuximab with β emitting luteium-177 ( 177 Lu-girentuximab) enables targeted delivery to CAIX-expressing tumor cells. Phase 1 - 2 data of 177 Lu-girentuximab in patients with metastatic ccRCC suggest favorable safety, tolerability, and efficacy profile. 1,2,3 LUTEON is a Phase 3 study designed to assess safety and efficacy of 177 Lu-girentuximab in patients with advanced, relapsed or recurrent ccRCC. Methods: LUTEON is a 2-part, randomized, open-label, multicenter study to determine the optimal activity and schedule of 177 Lu-girentuximab (Part 1), and evaluate efficacy and safety of 177 Lu-girentuximab versus an approved monotherapy standard-of-care (SOC) comparator (Part 2). Eligible patients are aged ≥18 years, have relapsed or recurrent, locally advanced or metastatic, histologically or cytologically confirmed ccRCC, and have received 2-3 prior lines of systemic therapies (including a PD-1/PD-L1 inhibitor and a VEGF/VEGFR-targeting agent) for locally advanced or metastatic ccRCC. Patients must have CAIX-positive cancer as determined by 89 Zr-girentuximab PET (performed during screening). In Part 1, patients will be randomized 1:1 (≤20/arm) to receive either 3 IV infusions of 1887 MBq 177 Lu-girentuximab every 8 weeks or 6 infusions of 1258 MBq 177 Lu-girentuximab every 4 weeks. Unacceptable toxicity is managed with predefined, clinically appropriate measures. In Part 2, patients will be randomized 1:1 to receive 177 Lu-girentuximab at the optimal regimen identified in Part 1 or an SOC comparator. In both parts, the end of treatment (EOT) visit occurs 3 ±1 week after the last infusion or within 30 days of discontinuing treatment. After EOT, efficacy assessments occur every 8 ±2 weeks for 6 months; patients will undergo tumor assessments according to RECIST 1.1 and will receive a contrast-enhanced CT and/or MRI of the chest, abdomen, and pelvis. In Part 2, after the first 6-month follow-up visits, patients continue follow-up every 12 ±2 weeks for up to 24 months after the EOT visit or until progression of disease, death, or the initiation of new systemic anticancer therapies, whichever occurs first. The primary endpoints of Part 1 are incidence and severity of TEAEs, patient discontinuation due to TEAEs, and dosing delays due to TEAEs. The primary endpoint of Part 2 is progression-free survival, defined as time from randomization to first disease progression according to RECIST 1.1 or death due to any cause. This study is sponsored by Telix Pharmaceuticals. Clinical trial information: NCT07197580 .