EAU 2025: A Phase I/II Study of Neoadjuvant, Intra-Arterial Administration of (177Lu) Lutetium Vipivotid Tetraxetan in Subjects with High-Risk, Localised or Locally Advanced Prostate Cancer (LUPUS)

(UroToday.com) The 2025 European Association of Urology (EAU) Annual Meeting held in Madrid, Spain between March 21st and 24th 2025, was host to the Abstract Session 05: On the Horizon: Ongoing Trials in Urology. Dr. Claudia Kesch presented Abstract A0079: A phase I/II study of neoadjuvant, intra-arterial administration of (177Lu) lutetium vipivotid tetraxetan in subjects with high-risk, localised or locally advanced prostate cancer (LUPUS).

LUPUS is a two-stage phase I/II safety and feasibility study evaluating (¹⁷⁷Lu)-Lutetium vipivotide tetraxetan as a pelvic intra-arterial infusion (internal iliac artery) in men with localized or locally advanced high-risk prostate cancer who are candidates for radical prostatectomy. Eligible patients must have at least one high-risk feature, including Gleason score ≥ 4+4=8, PSA ≥ 20 ng/mL, extracapsular extension on mpMRI/PSMA-PET, or cN+ disease on mpMRI/PSMA-PET.

  • Gleason Score ≥ 4+4=8 and/or
  • PSA ≥ 20 ng/mL and/or
  • Extracapsular extension (mpMRI/PSMA-PET) and/or
  • cN+ (mpMRI/PSMA-PET)

In the first stage, 10 patients will receive a single cycle of 200 mCi (7.4 GBq) of (¹⁷⁷Lu)-Lutetium vipivotide tetraxetan. If ≥4 of these 10 patients experience a delay in surgery or CTCAE Grade ≥3 adverse events (AEs) due to treatment, the study will be terminated. Otherwise, an additional 10 patients will be enrolled in the second stage and receive a single cycle of 400 mCi (14.8 GBq) of (¹⁷⁷Lu)-Lutetium vipivotide tetraxetan. At six weeks, patients will be reassessed and undergo radical prostatectomy.
The primary endpoint of the study is feasibility. Intra-arterial (¹⁷⁷Lu)-Lutetium vipivotide tetraxetan therapy will be considered not feasible if ≥40% of patients require a delay in surgery due to treatment-related adverse events (AEs) or experience Grade ≥3 treatment-related AEs.

Key Secondary Endpoints include:

  • PSA response
  • Pathologic response as measured by pathological complete response (pCR)
  • Minimal residual disease (MRD), defined as a tumour burden of ≤5 mm in greatest dimension

Other Endpoints are summarized below:
Other Endpoints
Dr. Kesch mentioned that for inclusion criteria they will only be enrolling patients with PSMA-positive disease on initial PSMA PET and concluded that LUPUS is the first trial investigating (177Lu) Lutetium vipivotide tetraxetan intra-arterial infusions and will help to evaluate if there is a role for neoadjuvant radioligand therapy in high-risk prostate cancer and if intra-arterial administration is the way to go.

Presented by: Claudia Verena Kesch, MD, Department of Urology, University Hospital Essen, Essen German Cancer Consortium (DKTK) University Hospital Essen, Essen, Germany

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 European Association of Urology (EAU) Annual Meeting held in Madrid, Spain between March 21st and 24th 2025