UPDATE: Phase 1 Trial of Alpha Radioligand Therapy AB001 in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

A new Phase 1 clinical study, known as the ARTISAN trial, is evaluating an investigational lead-212 alpha radioligand therapy targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC).

We discussed AB001 in a previous article; the trial has now been approved, and its full details are available.

The therapy combines a PSMA-targeted small molecule with the alpha-emitting isotope lead-212 (²¹²Pb). Alpha particles deliver highly localized, high-energy radiation, limiting exposure to surrounding healthy tissue. This precision approach is designed to improve tumor targeting while reducing systemic side effects often associated with conventional radiotherapy.

With a half-life of 10.6 hours, ²¹²Pb aligns well with the biological activity of small peptides used in targeted radiopharmaceuticals. Preclinical findings suggest stronger tumor control compared with beta-emitting agents like 177Lu-PSMA (Pluvicto), particularly when treatment is administered in fractionated doses rather than a single high dose.

This is the first clinical evaluation of a PSMA-targeted therapy using lead-212, introducing alpha-emitting technology into a treatment space previously dominated by beta-based radioligands. By including both 177Lu-PSMA–naïve and previously treated patients, the trial seeks to address an unmet need for individuals who progress following standard radioligand therapy.

Approximately 80 participants will be enrolled at multiple sites in the United States, with potential expansion abroad.

Primary endpoints include safety, tolerability, and identification of the optimal dose and schedule.
Secondary endpoints include PSA decline rates (PSA50 and PSA90 responses), objective response rate, radiographic progression-free survival, and pharmacokinetic and imaging assessments.

Early-phase studies in a small number of patients indicated acceptable safety and promising biodistribution, with notable tumor uptake and limited off-target accumulation.

Clinical trial.