Trial launches of actinium (225Ac) rhPSMA-10.1 injection in mCRPC

The first patient has been dosed in a phase 1 study (NCT07414940) of actinium (²²⁵Ac) rhPSMA-10.1 injection, an investigational alpha‑emitting prostate-specific membrane antigen (PSMA)‑targeted radiopharmaceutical for metastatic castration‑resistant prostate cancer (mCRPC).¹

Actinium-225 is an alpha-emitting radionuclide, which are designed to deliver a high amount of energy over a very short tissue range to produce more efficient double-strand DNA breaks in targeted cancer cells. When combined with the PSMA-targeting molecule rhPSMA-10.1, the approach is intended to offer a targeted treatment strategy with limited radiation exposure to surrounding tissue.

"This study is an important step in advancing more precise treatment options for men with metastatic castrate-resistant prostate cancer,” said Gerhardt Attard, MD, PhD, FRCP, chair in urological cancer research at University College London (UCL), in a news release.¹ “The combination of a highly targeted PSMA approach with the potent, short-range effects of an alpha-emitting radionuclide offers a promising strategy to deliver meaningful anti-tumor activity while limiting toxicity. Early-phase trials such as this are essential for determining safety, refining dose and guiding how these therapies can be integrated into personalized treatment pathways to improve outcomes for patients."

How is the phase 1 study of ²²⁵Ac rhPSMA-10.1 injection designed?

The phase 1 trial, also known as ACT-RESoLUTE, is designed to assess the safety and preliminary anti-tumor activity of ²²⁵Ac rhPSMA-10.1 injection in patients with PSMA‑positive mCRPC whose disease has progressed following prior therapy. Investigators are enrolling patients through UCL.

To be eligible for enrollment, patients need to have prior treatment with at least 1 second-generation androgen receptor pathway inhibitor and at least 1 but no more than 2 lines of prior taxane therapy. Participants must also have PSMA-avid disease on PSMA-PET, an ECOG performance score of 0 or 1, and no worse than grade 1 xerostomia symptoms at baseline.

Investigators plan to enroll up to 60 patients in the trial, all of whom will receive a dose of ²²⁵Ac-rhPSMA-10.1 injection every 6 weeks to a maximum of 6 doses. Phase 1 of the study will follow a dose escalation design. After determination of a recommended phase 2 dose, the study will proceed to the dose expansion portion.

The primary end point is the incidence of dose-limiting toxicities (in phase 1) and preliminary anti-tumor responses (in phase 2). Study completion is expected in 2031.

What is the clinical context around this agent?

²²⁵Ac rhPSMA-10.1 injection builds on Blue Earth’s existing clinical program for lutetium (¹⁷⁷Lu) rhPSMA‑10.1 injection. The beta-emitting radiopharmaceutical is currently being assessed in a phase 2 clinical trial in patients with mCRPC. Results from phase 1 of the study were shared in June 2025, showing that ¹⁷⁷Lu rhPSMA-10.1 injection delivered proportionally higher absorbed radiation doses in tumors than in normal organs, supporting effective tumor targeting.

Related: 177Lu-rhPSMA-10.1 injection shows positive radiation dosimetry results in mCRPC

"Initiation of this collaborative phase 1 study represents an important milestone for Blue Earth Therapeutics and our investigational radiopharmaceutical therapy pipeline," said David Gauden, CEO of Blue Earth Therapeutics, in the news release.¹ "Building on our clinical experience in both alpha‑ and beta‑emitting radiopharmaceutical therapies, we are combining the targeting precision of rhPSMA with the alpha‑emitting properties of actinium‑225 to explore a potential treatment approach for patients with advanced prostate cancer. We are very grateful to the team at UCL and to their patients for undertaking this study."

REFERENCES

1. Blue Earth Therapeutics announces first participant dosed in Phase 1 clinical trial investigating Actinium (²²⁵Ac) rhPSMA-10.1 Injection in metastatic castration-resistant prostate cancer. News release. Blue Earth Therapeutics. July 9, 2026. Accessed July 9, 2026. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-announces-first-participant-dosed-in-phase-1-clinical-trial-investigating-actinium-ac-rhpsma-10-1-injection-in-metastatic-castration-resistant-prostate-cancer-302820625.html

2. ACTinium in Castrate-RESistant Prostate Cancer After LUTEtium (ACT-RESoLUTE). ClinicalTrials.gov. Last updated May 8, 2026. Accessed July 9, 2026. https://clinicaltrials.gov/study/NCT07414940