ASCO 2021: Early-Phase Study of Alpha Emitter in Castration-Resistant Prostate Cancer
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 coi.asco.org.
