RENALUT trial

Prof Emmanuel Seront presented the RENALUT trial, an international, multicenter phase 2 study led by the EORTC, designed to explore a novel therapeutic strategy for mccRCC. In this disease, which is characterised by a highly angiogenic tumour biology, first-line treatment typically consists of IO–TKI combinations or dual immunotherapy. Although these regimens have improved outcomes, most patients ultimately relapse and require subsequent systemic therapy, where available options remain limited and ORR rarely exceed 30%.

The RENALUT trial investigates the therapeutic repositioning of 177Lu-PSMA, a radioligand therapy already established in prostate cancer. PSMA is also strongly expressed in the tumour-associated vasculature of ccRCC. This provides a rational biological target and an alternative mechanism for anti-angiogenic therapy. Eligible patients must have progressed after prior IO–TKI or IO–IO therapy, and all must have received both an ICI and a VEGFR-targeted TKI. Before enrolment, patients undergo PSMA imaging to confirm PSMA-positive metastatic lesions, ensuring appropriate biological selection.

Participants receive four cycles of 177Lu-PSMA administered every six weeks, with the option of two additional cycles in cases of partial response or stable disease. Tumour response is assessed using standard imaging modalities. The trial aims for an objective response rate of at least 30%, recognising that this represents the first prospective evaluation of PSMA-targeted radioligand therapy in renal cancer and may open an entirely new therapeutic avenue.