A phase I/II study of neoadjuvant, intra-arterial administration of (177Lu)lutetium vipivotide tetraxetan in subjects with high-risk, localised or locally advanced prostate cancer (LUPUS).

TPS431 Background: The recent LuTectomy trial suggested that intra-venous [177Lu]Lu-PSMA-617 prior to surgery in men with high-risk localised or locally advanced prostate cancer (HRCaP) is safe and effective. We hypothesise that intra-arterial infusion will further enhance target lesion uptake and efficacy without compromising safety. LUPUS is the first trial investigating (177Lu)Lutetium vipivotide tetraxetan intra-arterial infusion and will help to further evaluate if there is a role for neoadjuvant radioligand therapy in HRCaP. Methods: Phase I/II study of neoadjuvant, pre-surgical (177Lu)Lutetium vipivotide tetraxetan as intra-arterial infusion in men with HRCaP who are candidates for radical prostatectomy (EU CTR 2022-500838-28-00). Intra-arterial perfusion is performed via a catheter into A. iliaca interna without concomitant embolization. In the first cohort, 10 patients will receive one cycle of 200 mCi (7.4 GBq) (177Lu)Lutetium vipivotide tetraxetan followed by radical prostatectomy 6 weeks thereafter. If less than 4 out of 10 patients have to delay surgery or suffer from CTCAE Grade ≥3 adverse events (AEs) due to the treatment, 10 additional patients will be included and receive one cycle of 400 mCi (14.8 GBq) (177Lu)Lutetium vipivotide tetraxetan. Enrolment began in September 2024. Primary endpoints are AEs and days of delay of scheduled surgery related to intra-arterial (177Lu)Lutetium vipivotide tetraxetan therapy. Secondary endpoints are PSA-response and pathological response. Other endpoints include imaging changes, changes in quality of life and dosimetry. Clinical trial information: EU Clinical Trial no.: 2022-500838-28-00 .