Dr. Tagawa on Ongoing Research With 225Ac-J591 in mCRPC

Scott T. Tagawa, MD, MS, Richard A. Stratton Associate Professor in Hematology and Oncology, associate professor of clinical medicine and urology at Weill Cornell Medicine, and associate attending physician, Weill Cornell Medical Center/NewYork-Presbyterian Hospital, discusses ongoing research with ²²⁵Ac-J591 in metastatic castration-resistant prostate cancer.

Prostate-specific membrane antigen (PSMA)-targeted small molecules, which are not specific to malignant PSMA cells, can cause mild adverse events when paired with beta emitters, such as dry mouth. However, these AEs tend to resolve, says Tagawa. If a small molecule is paired with an alpha emitter, it can cause severe damage to salivary glands and, in the most extreme cases, loss of taste as well as loss of teeth.

Therefore, in a phase I dose-escalation trial, investigators paired the alpha emitter ²²⁵Ac with an antibody, rather than a small molecule. The alpha emitter, which is more powerful than a beta emitter, travels at a shorter distance, so it does not pose as much risk to the patient’s kidneys, bowels, and salivary glands. Investigators evaluated 7 different dose levels and were able to reach the seventh dose level without a dose-limiting toxicity, says Tagawa. As such, the seventh dose is the recommended phase II dose that will be evaluated in future studies alone, and in combination, concludes Tagawa.