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Phase I Study of PSMA Targeted 225Ac-J591 Reveals Tolerability in mCRPC
In an ongoing phase I dose-escalation trial, 225Ac-J591 was evaluated as a highly potent PSMA targeted therapy for researchers to determine the highest dose level patients with progressive metastatic castration-resistant prostate cancer could receive without severe side effects.
“Antibodies and small molecule ligands target PSMA with different kinetics and biodistribution. Alpha emitters such as 225Ac have high potency, but short range. We report dose-escalation plus cohort results of a first in human study of 225Ac-J591,” explained Scott Tagawa, MD, MS, FACP, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, alongside co-investigators.
Researchers found that standard treatments for prostate cancer that spread beyond the prostate gland intend to minimize adverse effects. However, such treatments are not curative.
Patients were eligible for enrollment upon diagnosis of progressive mCRPC following at least 1 potent AR-pathway inhibitor and chemotherapy session with adequate organ function.
All 31 participants received a single dose of 255Ac-J591 on 7 dose levels with expansion at the highest dose level. Clinical data from the study shows the median age of patients was 69.5, PSA 149.1, 75% with >2 prior ARPI, 62.5% chemo, 28% Ra-223, 43.7% 177Lu-PSMA.
Change in the number of subjects with dose limiting toxicities (DLT) and maximum tolerated dose (MTD) were primary endpoints. DLTs were measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE).
Following a single dose of 255Ac-J591, median PFS 7.2 months (95% CI, 4.6), median OS 10.9 months (95% CI, 7.6-21.1).
“PSMA-targeted alpha-emitter255Acutilizing intact antibody J591 is tolerable with early evidence of clinical activity. Based on these results, a follow up study testing multiple and fractionated dosing of 225Ac-J591 is underway,” concluded Dr Tagawa et al. – Alexa Stoia
