Prostate Cancer Coverage from Every Angle

ASCO 2021: Early-Phase Study of Alpha Emitter in Castration-Resistant Prostate Cancer

By: Vanessa A. Carter, BS
Posted: Thursday, June 17, 2021

Scott T. Tagawa, MD, of Weill Cornell Medicine, New York, and colleagues presented reportedly the first in-human study of the targeted radionuclide 225Ac-J591 for individuals with castration-resistant prostate cancer during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5015). The investigators reported that the combination of prostate-specific membrane antigen (PSMA)-targeted alpha-emitter 225Ac and intact antibody J591 showed early evidence of clinical activity, with an ongoing follow-up study testing various dose levels.

This phase I study enrolled 32 men with progressive metastatic castration-resistant prostate cancer who received at least 1 potent androgen receptor–pathway inhibitor and any number of prior chemotherapies. Participants were administered 225Ac-J591 at seven dose levels, starting from 13.3 KBq/kg and escalating to 93.3 KBq/kg.

The median patient age was 69.5 years, and the median prostate-specific antigen (PSA) level was 149.1 ng/mL; 75% of participants received more than two prior androgen receptor–pathway inhibitors, and 62.5% received chemotherapy. A majority of individuals had poor-risk disease (n = 23), followed by intermediate- (n = 8) and good-risk disease (n = 1).

Grade 4 anemia and platelets were dose-limiting toxicities for one patient receiving a dose-level of 80 KBq/kg. Hematologic adverse events such as grade 3 platelet count and grade 3 neutropenia affected four and two individuals, respectively; nonhematologic adverse events such as grade 1 to 2 nausea (43.7%), aspartate transaminase increase (37.5%), fatigue (31.2%), and grade 1 xerostomia (25%) were also observed.

A decline in PSA levels was observed in 68.7% of patients, with 37.5% showing a decline of more than 50%. By week 12, pain scores appeared to improve, but circulating tumor cell levels declined in 12 patients, with 5 remaining at 0 and 4 showing an elevation. Of note, after a single dose of 225Ac-J591, the median progression-free survival was 7.2 months, and the median overall survival was 10.9 months.

Disclosure: For full disclosures of the study authors, visit

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.