First Site Activated in EORTC RENALUT Clinical Trial on Metastatic Clear Cell Renal Cell Carcinoma

The European Organisation for Research and Treatment of Cancer (EORTC) has activated the first site for the EORTC-2361-GUCG RENALUT clinical trial. This phase II, single-arm, multicentre study investigates the potential of Pluvicto (177Lu]Lu‑PSMA‑617) as a new treatment option for patients with metastatic clear cell renal cell carcinoma (ccRCC) who have progressed after one or two previous systemic therapies.

About ccRCC

Clear cell renal cell carcinoma is the most common subtype of kidney cancer and is often driven by mutations in the Von Hippel-Lindau (VHL) gene, contributing to the tumours highly vascular nature. Most patients today receive combinations or sequences of immunotherapy and targeted therapies, such as VEGFR tyrosine kinase inhibitors. However, after progression on these regimens, options are limited. This highlights the need for new therapeutic strategies for patients in later lines of treatment.

About the RENALUT study

The RENALUT trial explores a novel therapeutic approach for metastatic ccRCC by leveraging radioligand therapy (RLT) targeting PSMA (prostate-specific membrane antigen). Although PSMA is best known for its role in prostate cancer, it is also expressed in the tumour neovasculature of ccRCC, making it a promising therapeutic target1. PSMA‑targeted imaging has shown strong performance in identifying metastatic ccRCC, supporting the idea that PSMA‑directed therapy with [177Lu]Lu‑PSMA‑617 may also be an effective treatment for this disease2,3. By building on the established use of [177Lu]Lu‑PSMA‑617 in metastatic castration resistant prostate cancer, RENALUT aims to determine whether this approach can benefit ccRCC patients who have exhausted standard treatments and currently face very limited options.

Participating sites and collaboration

The activation of the first site marks a significant milestone for this innovative trial, which will involve 11 centres across Europe. The study is led by EORTC’s Genito-Urinary Cancer Group (GUCG) and supported by a network of international collaborators.

By exploring PSMA-targeted RLT in ccRCC, RENALUT aims to address an urgent unmet need and pave the way for future treatment strategies in kidney cancer.

1. Watanabe R, Kagimoto K, Chosei M, et al. Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression. Cells 2025;14(3):165.
2. Urso L, Castello A, Rocca GC, et al. Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives. J Cancer Res Clin Oncol 2022;148(6):1299–311.
3. Gasparro D, Scarlattei M, Silini EM, et al. High Prognostic Value of (68)Ga-PSMA PET/CT in Renal Cell Carcinoma and Association with PSMA Expression Assessed by Immunohistochemistry. Diagnostics (Basel) [Internet] 2023;13(19). Available from: https://www.ncbi.nlm.nih.gov/pubmed/37835825