(UroToday.com) The 2025 ESMO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Oliver Sartor discussing the ARTISIAN trial, a phase 1/2 dose escalation and expansion trial of AB001 in patients with metastatic castration-resistant prostate cancer (mCRPC).
Treatment options for patients with mCRPC have been improved by radioligand therapies, such as beta-emitting 177Lu-PSMA-617. However, prostate cancer remains the fifth leading cause of cancer mortality, with the lives of more than 250,000 men claimed by mCRPC each year. New therapies with differentiated mechanisms of action that could extend survival while retaining quality of life are needed.
Alpha-particle-emitting radioisotopes offer significant advantages compared with beta-emitters. Alpha particles have a higher atomic mass (4), charge (2+), and linear energy transfer. Furthermore, the short particle range (<100 μm) is expected to minimize damage to surrounding normal tissue. 212Pb is attractive for alpha radiotherapeutics due to its short 10.6-hour half-life, fitting well with the rapid tumor uptake achievable with PSMA-targeting small molecules. The 212Pb decay scheme is highlighted as follows:
The ARTISAN trial is a dose escalation expansion study of AB001, a 212Pb-labelled, PSMA-targeted small molecule alpha-radiotherapeutic.
This is a phase 1/2, open-label, multicenter study in patients with advanced PSMA-positive mCRPC. Participants must have received previous treatment with at least one androgen receptor pathway inhibitor and at least one but no more than two prior taxanes. Dose escalation will evaluate the safety and tolerability of AB001 in participants with mCRPC who have not received prior treatment with 177Lu-PSMA radioligand therapy, and identify the recommended dose and schedule for dose expansion. A time-to-event Bayesian optimal interval design is employed to allow dosage optimization by both escalation of the 212Pb radioactive dose (MBq) and assessment of optimal cycle duration:
Dose expansion will further evaluate safety, tolerability, and preliminary activity of AB001 in two populations:
Group A: participants who have not received prior treatment with 177Lu-PSMA
Group B: participants who have been treated with 177Lu-PSMA
Assessment of AB001 biodistribution and dosimetry estimation by 212Pb SPECT imaging will be used in addition to radioactive and ligand pharmacokinetic evaluation to enable efficient dosage optimization of AB001 in this phase 1/2 trial.
Clinical trial identification: 2024-516523-14
Presented by: A. Oliver Sartor, MD, Director, Transformational Prostate Cancer Research Center, East Jefferson General Hospital Cancer Center, Tulane University Cancer Center, New Orleans, LA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 European Society of Medical Oncology (ESMO) Annual Meeting, Berlin, Germany, Fri, Oct 17 – Tues, Oct 21, 2025.
Related content: ARTISAN Trial: Evaluating Lead-212 PSMA Therapy for Advanced Prostate Cancer - Oliver Sartor