Novartis goes earlier with actinium

Earlier this year Novartis began the first pivotal trial of its actinium-labelled PSMA radiopharmaceutical Ac-PSMA-617; now a new phase 3 will test the project in an earlier prostate cancer niche. The previously revealed phase 2/3, PSMAction, is enrolling castration-resistant prostate cancer patients who’ve already received an androgen receptor pathway inhibitor like Zytiga or Xtandi, chemo and Novartis’s approved lutetium labelled PSMA-targeted therapy, Pluvicto. Meanwhile, the upcoming phase 3, AcTFirst, will evaluate patients post-ARPI, but pre-Pluvicto and chemo. Pluvicto isn’t approved in the pre-chemo setting, but is due an FDA decision here in the first half of 2025, based on the PSMAfore trial. Perhaps this is why AcTFirst won’t compare Ac-PSMA-617 directly against Pluvicto, but rather against investigator’s choice of ARPI switch or chemo. Still, the study isn’t due to start until August, by which time Pluvicto might have the nod. Alpha emitters like actinium are said to be more potent and precise than beta emitters like lutetium, but the jury is still out. Novartis also has another actinium shot on goal, via the earlier-stage Ac-PSMA-R2, while other players include AstraZeneca, via its purchase of Fusion, and Bristol Myers Squibb, courtesy of its RayzeBio buy.

Pivotal trials of 225Ac-PSMA-617

Note: ARPI=androgen receptor pathway inhibitor. Source: OncologyPipeline & clinicaltrials.gov.