Early Results With Alpha Emitter for Metastatic Castration-Resistant Prostate Cancer
Posted: Friday, July 31, 2020
Early evidence of clinical activity emerged from a first-in-human study of the prostate-specific membrane antigen (PSMA)-targeted alpha emitter 225Ac-J591, according to Neil H. Bander, MD, of Weill Cornell Medical College, New York, and colleagues during the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II (Abstract CT122). The phase I dose-escalation study focused on men with progressive metastatic castration-resistant prostate cancer and adequate organ function who had been treated with at least one androgen receptor–targeted agent, such as abiraterone/enzalutamide, and, for about two-thirds of the men, with chemotherapy as well.
Of the 22 patients (median age, 72.5 years) participating in the dose-escalation phase of the trial, 9 experienced a PSA decline of more than 50%, and 14 in total experienced any degree of PSA decline. The men were about equally divided between classification of their disease as intermediate and high prognostic risk, and one patient was included in the good prognostic risk category. The population tolerated the agent well, with just one patient experiencing a dose-limiting toxicity.
“Interestingly, 15 had [an] initial PSA increase followed by subsequent decline from peak,” said Dr. Bander and co-researchers. The most common low-grade adverse effects were fatigue, pain flare, and nausea, each affecting at least half of the men. Seven different doses were tested; the highest dose was 93.3 KBq/kg, which was given to six patients.
In follow-up, two men continued to respond to 225Ac-J591 for more than 1 year. As a result, “correlative studies are in progress, and enrollment into a Simon two-stage expansion cohort has been initiated,” the team stated.
Disclosure: For disclosures of the study authors, visit abstractsonline.com.