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ASCO 2026 | AcTION: Phase I trial of 225Ac-PSMA-617 radioligand therapy in mCRPC

Jeremie Calais, MD, PhD, University of California, Los Angeles, CA, presents Phase I dose-escalation findings from AcTION (NCT04597411), evaluating actinium-225-labeled PSMA-targeted radioligand therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), with or without prior lutetium-177 PSMA radioligand therapy. Results demonstrated a promising PSA response rate and acceptable safety profile across all dose groups and patient subgroups, with no dose-limiting toxicities observed. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.

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Transcript

The AcTION trial is a phase one trial of actinium-225, PSMA-617, a radioligand therapy for metastatic, castration-resistant prostate cancer patients. So they did a dose escalation to find the RPTD dose, which would be 10 megabecquerels. So that’s the main key finding, 10 megabecquerels per injected cycle. I think what is interesting is to realize how Actinium is very much more potent, delivers much more energy than Lutetium...

The AcTION trial is a phase one trial of actinium-225, PSMA-617, a radioligand therapy for metastatic, castration-resistant prostate cancer patients. So they did a dose escalation to find the RPTD dose, which would be 10 megabecquerels. So that’s the main key finding, 10 megabecquerels per injected cycle. I think what is interesting is to realize how Actinium is very much more potent, delivers much more energy than Lutetium. So 10 MBq compared to what we give with Lutetium 177 is 7.4 GBq. So we almost have like 700, 1000 times amount of injected activity difference. And that’s because Actinium is much more potent. So you need much less injected activity to have still a lot of energy delivered and damage created. So I think they were able to show safety and also promising efficacy data in three cohorts at different disease stages. And now they can move to the phase two trial.

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