Highlights from ASCO GU 2026: 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

How to cite: Saad F. Highlights from ASCO GU 2026: 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. Grand Rounds in Urology. February 2026. Accessed Feb 2026. https://grandroundsinurology.com/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

Summary

In this conversation with E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology, University of California, San Diego, San Diego, California, Fred Saad, MD, FRCS, CQ, FCAHS, Professor and Chair of Urology, Director of Genitourinary Oncology, and Director of Clinical Research and the Molecular Oncology Research Laboratory in Prostate Cancer, University of Montréal, Quebec, Canada, reviews early-phase clinical data on the alpha-emitting radioligand trillium and examines its potential role in metastatic castration-resistant prostate cancer (mCRPC) following androgen receptor pathway inhibitor and taxane therapy.

The therapeutic rationale builds on prior experience with beta-emitting radioligand therapy and radium-223. Dr. Saad describes the ongoing need for agents with potent tumor cell kill rate and reduced off-target toxicity, particularly involving salivary glands and renal exposure.

The trillium construct incorporates a macroparticle strategy intended to reduce off-target effects while preserving efficacy. The phase 1 trial used dose escalation from 75 to 150 millicuries across four dose levels, administered every six weeks for up to four cycles. No dose-limiting toxicities were observed, and 80% of patients completed all four cycles. Adverse events were primarily grade 1 to 2, including xerostomia and nausea, with no grade 3 or 4 salivary toxicities reported.

Although designed to assess safety, the study demonstrated encouraging efficacy signals. Prostate-specific antigen (PSA) declines of at least 50% occurred across dose levels. At the 125 dose level, 83% of patients achieved a 50% decline, and 67% achieved a 90% decline. Measurable soft-tissue response rates reached 71%. All participants had received at least one androgen receptor pathway inhibitor and one taxane, with some exposed to multiple taxanes. Expansion cohorts now include taxane-naïve patients and those previously treated with radioligand therapy, including lutetium, to address sequencing considerations in the post-lutetium setting.