EAU 2025: A Phase 3 Study with Standard of Care with and Without 177Lu-Rosopatamab (TLX591) for Patients with Metastatic Castration-Resistant Prostate Cancer Progressing Despite Treatment with a Novel Androgen Axis Drug (ProstACT GLOBAL)

(UroToday.com) The 2025 European Association of Urology (EAU) Annual Meeting held in Madrid, Spain between March 21^st and 24^th 2025, was host to the Abstract Session 05: On the Horizon: Ongoing Trials in Urology. Dr. Martina Sollini on behalf of Dr. Sartor presented Abstract A0080: A Phase 3 Study with standard of care with and without 177Lu-rosopatamab (TLX591) for patients with metastatic castration-resistant prostate cancer progressing despite treatment with a novel androgen axis drug (ProstACT GLOBAL)

[¹⁷⁷Lu]Lu-rosopatamab is a radiolabeled antibody-drug conjugate (rADC) designed for PSMA-expressing mCRPC. It employs a PSMA-targeted monoclonal antibody (mAb) approach, leveraging PSMA as a validated target for prostate cancer theranostics. mAbs are characterized by their ability to internalize, exhibit long retention, and demonstrate functional selectivity for tumor-expressed PSMA.

These characteristics grant [¹⁷⁷Lu]Lu-rosopatamab favorable biodistribution properties, offering several advantages as a tracer. It exhibits high PSMA binding specificity, with minimal off-tumor organ diffusion limited to the liver and spleen, and primarily undergoes hepatic excretion, as demonstrated below.

The ProstACT Global trial is a prospective, open-label Phase 3 study designed to enroll PSMA+ mCRPC patients who have progressed on ARPI (abiraterone, apalutamide, darolutamide, enzalutamide) in either the mCSPC or mCRPC setting. Patients may have received prior docetaxel in the mCSPC setting, provided the last dose was ≥6 months before screening. The study aims to enroll 520 men and is structured in two parts: a dosimetry and safety lead-in phase, followed by a randomized treatment expansion phase, as illustrated below.

The first part of the study focuses on dosimetry and safety, enrolling 30 patients who receive two treatments administered 14 days apart. The primary endpoints for this phase include dosimetry assessments and adverse events.

Part 2 is the randomized treatment expansion. Dr. Sollini mentioned the standard of care would be an ARPI switch or docetaxel
Detailed inclusion criteria are outlined below:


The trial is currently recruiting patients in the US, New Zealand, and Australia and they are planning to start in Europe in the upcoming months.

Presented by: Martina Sollini, MD, Associate Professor in Diagnostic Imaging and Radiotherapy, Vita-Salute San Raffaele University, Nuclear Medicine Physician at Arcispedale Santa Maria Nuova – IRCCS, Milan, Italy. 

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 21^st and 24^th 2025