Prof Fred Saad speaks to ecancer about the first-in-human assessment of actinium-225-prostate-specific membrane antigen (225Ac-PSMA)-Trillium (BAY 3563254) in mCRPC: Dose-escalation results of the phase 1 PAnTHa study.

This trial evaluated 225Ac-PSMA-Trillium, a novel prostate-specific membrane antigen-targeting alpha-emitter therapy, in patients with metastatic castration-resistant prostate cancer who had previously been treated with androgen receptor pathway inhibitors and, if eligible, taxanes.

In 50 patients across escalating dose cohorts ranging from 75 to 150 kBq/kg, no dose-limiting toxicities or treatment-related deaths were observed. Treatment-emergent adverse events were mostly low-grade, with dry mouth occurring in 76 percent of patients, fatigue in 48 percent, and nausea in 44 percent.

Prof Saad says that among patients with measurable disease, the overall response rate was 46 percent, with a disease control rate of 83 percent.

At the recommended dose for expansion of 125 kBq/kg, PSA50 and PSA90 response rates were 83 percent and 58 percent, respectively.

Notably, patients with high baseline prostate-specific membrane antigen expression, defined as a standardised uptake value mean greater than 10, had PSA50 responses in 93 percent of cases.

Prof Saad concludes that these results demonstrate that 225Ac-PSMA-Trillium is well-tolerated and highly active, supporting further clinical investigation in metastatic castration-resistant prostate cancer.