Phase 1 PAnTHa Trial: mCRPC First Data

²²⁵Ac‑PSMA‑Trillium (BAY3563254) is an experimental treatment that delivers targeted alpha radiation to prostate cancer cells. It combines a highly selective PSMA‑binding molecule with an albumin‑binding domain that helps it stay in the bloodstream longer and reach tumors more effectively. The radioactive component, actinium‑225, is attached using a stable Macropa chelator to increase safety and stability.

In the global Phase 1 PAnTHa trial, 50 men with advanced prostate cancer received intravenous doses every six weeks, up to four treatments. The main goal was to assess safety and find the best dose for future studies, while also tracking signs of tumor response.

The safety profile was encouraging. No dose‑limiting toxicities or treatment‑related deaths occurred. Most patients experienced mild or moderate side effects, mainly dry mouth, fatigue, or nausea. This represents a marked improvement compared with older actinium‑based PSMA therapies, which often caused more severe salivary gland and marrow issues.

²²⁵Ac‑PSMA‑Trillium also showed strong anticancer activity. Among patients with measurable tumors, 46% had notable tumor shrinkage, and disease control was seen in 83%. PSA responses were particularly striking: at the selected recommended dose of 125 kBq/kg, 83% of men achieved at least a 50% drop in PSA and 58% achieved a 90% reduction. Responses were most pronounced in patients whose PSMA‑PET scans showed high levels of target expression. Early analysis of circulating tumor DNA confirmed this pattern, showing rapid and dose‑related reductions after treatment began.

Clinical trial.