A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha…

Cohort studyClinical cancer research : an official journal of the American Association for Cancer Research· Jul 2026

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.

Scott T Tagawa, Charlene Thomas, Abdul Baseet Arham … Joseph Osborne

HematologyCohort studyTreatmentQ1IF 9.3

Fractionated 225Ac-J591 dosing showed prostate-specific antigen decline in 60% of patients.

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.

Scott T Tagawa … Joseph Osborne

Clinical cancer research · Jul 2026

Purpose

To test safety of two regimens at differing levels of radioactivity of PSMA-targeted alpha radionuclide 225Ac-J591.

Methods

With progressive, metastatic androgen pathway modulator resistant prostate cancer were enrolled in two parallel dose-escalation cohorts: (1) fractionated-dose regimen (single cycle of 45 - 65 KBq/kg of 225Ac-J591 on day 1 and day 15; main cohort agnostic to prior receipt of 177Lu-PSMA, additional cohort post 177Lu-PSMA) and (2) multiple cycles of 225Ac-J591 (45 - 65 KBq/kg administered every 6 weeks for up to 4 cycles).

n = 42 patients

Results

patients had a significant drop in their PSA levels, a prostate cancer marker

fractionated cohorts

60%

multiple cycle

28%

More results

All received > 1 prior AR pathway inhibitor, 72% chemotherapy, 18% 177Lu-PSMA.

Seven had dose-limiting toxicity in multiple cycle regimen; this regimen is not recommended for further development.

More results

Amongst adverse events of special interest, temporary hematologic toxicity was most common [93% thrombocytopenia (32% grade >3), 65% neutropenia (13% grade >3), 63% anemia (20% grade >3)]; dry mouth occurred in 62% (2% grade 2).

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Conclusion

Fractionated dosing of 225Ac-J591 appears promising. Further investigation is underway.

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.

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