Phase 1 225Ac-J591 Trial: Strong Activity in Advanced Prostate Cancer, with Improved Outcomes Using a Fractionated Dosing Approach

225Ac-J591 (Actinium-225 rosopatamab tetraxetan) uses a radioactive particle linked to an antibody that targets PSMA, a protein found on prostate cancer cells, and it is being studied in a phase 1 clinical trial. Unlike more commonly used PSMA treatments that rely on small molecules, this approach uses an antibody, which behaves differently in the body. It moves more slowly and reaches tumors through the bloodstream in a different way.

Researchers treated 60 patients with advanced, heavily pretreated prostate cancer. Many had already received hormone therapies and chemotherapy, and some had also been treated with other radioligand therapies (Pluvicto). The study compared two strategies: a standard schedule with doses given weeks apart, and a “fractionated” approach where two doses were given closer together.

The difference turned out to be important. Patients who received the fractionated treatment had better outcomes across several measures. About 68% of patients experienced a PSA decline of more than 50%, which is considered a strong response in this setting. In addition, 61% showed a reduction in circulating tumor cells, and over a third converted from unfavorable to more favorable levels.

These responses translated into clinical benefit. Median progression-free survival was 5.2 months, and overall survival reached 15.4 months in this heavily pretreated group. Both measures were significantly better with the fractionated schedule compared to the standard approach.

By contrast, the standard schedule proved difficult to maintain. Blood-related side effects, especially low platelet counts, often delayed treatment cycles. This made it challenging to deliver therapy as planned and ultimately limited its effectiveness.

Side effects were mainly hematologic, as expected with this type of therapy. Despite this, overall quality of life remained stable during treatment, and pain scores tended to improve, suggesting that patients still experienced meaningful clinical benefit.

Overall, this study suggests that 225Ac-J591 is a promising option for patients with advanced prostate cancer, particularly when given in a carefully timed, fractionated schedule. A larger, multicenter trial is now underway to confirm these findings and better define its role in treatment.

Source.

Clinical trial.