84 Phase 3 Study to Assess the Safety and Efficacy of 177Lu-girentuximab in Advanced, Relapsed or Recurrent ccRCC (LUTEON; NCT07197580)

Abstract 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 CAIX, expressed on > 95% ccRCC cells (limited expression in healthy tissues). Radiolabeling girentuximab with β-emitting lutetium-177 (177Lu-girentuximab) enables targeted delivery to CAIX-expressing tumor cells. Phase 1/2 data suggest favorable safety, tolerability, and efficacy profile.1,2,3 LUTEON is a Phase 3 study to assess safety and efficacy of 177Lu-girentuximab in patients with advanced, relapsed or recurrent ccRCC. Methods LUTEON is a 2-part, randomized, open-label, multicenter Phase 3 study, including an initial dose-optimization component (Part 1) followed by an efficacy and safety evaluation (Part 2). Eligible patients will be ≥ 18y; have relapsed or recurrent, locally advanced or metastatic, histologically or cytologically confirmed ccRCC; and have received 2-3 prior lines of systemic therapies for locally advanced or metastatic ccRCC. Patients must have CAIX-positive cancer as determined by 89Zr-girentuximab PET. In Part 1, patients are randomized 1:1 (≤20/arm) to receive either 3 IV infusions of 1887MBq 177Lu-girentuximab every 8wks or 6 infusions of 1258MBq 177Lu-girentuximab every 4wks. Unacceptable toxicity is managed with prespecified, clinically appropriate measures. In Part 2, patients will be randomized 1:1 to receive 177Lu-girentuximab at optimal regimen identified in Part 1 or SOC comparator. In both parts, end of treatment (EOT) visit occurs 3±1wk after the last infusion of 177Lu-girentuximab or within 30d of discontinuing. After EOT, efficacy assessments occur every 8±2wks for 6m; patients will undergo tumor assessments according to RECIST 1.1 and will receive contrast-enhanced CT and/or MRI of chest, abdomen, and pelvis. In Part 2, after first 6-m follow-ups, patients will continue follow-up every 12±2wks for up to 24m after EOT visit or until progression, death, or initiation of new systemic anticancer therapies, whichever occurs first. The primary objective of Part 1 is to select the recommended Phase 3 dose (RP3D) to be administered in Part 2 from the two dose regimens administered in Part 1. The primary objective of Part 2 is to compare the median progression-free survival of treatment with 177Lu-girentuximab with that of the comparator as assessed by blinded independent central review. Results Rapid disease progression experienced by patients in late-line ccRCC necessitates improved therapeutic options. Previous study results support further investigation into efficacy of 177Lu-girentuximab in these patients. References: Stillebroer 2012 JNM; Stillebroer 2013 EurUrol; Muselaers 2016 EurUrol Conclusions N/A