Scott Tagawa, MD, on the mechanism of action for 177Lu-TLX591 in mCRPC

In this video, Scott T. Tagawa, MD, MS, FACP, FASCO, speculates on the mechanism of action for 177Lu-TLX591 (¹⁷⁷Lu-DOTA-rosopatamab), which is being assessed in the phase 3 ProstACT GLOBAL trial (NCT06520345) in patients with metastatic castration-resistant prostate cancer (mCRPC). Tagawa is a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center in New York, New York.

Video Transcript:

It's radiation. We know that whether it's an antibody or small molecule, it will circulate, land, and bind to PSMA. I mentioned before the places that the antibody typically doesn't bind, like the salivary glands, but it binds to PSMA and then is internalized. That's one thing that is different in terms of antibody for small molecules, internalized and retained. Small molecules are internalized and externalized, but they can go in a neighboring cell, and whatever's attached to it is brought into the cell. In this case, the beta emitter lutetium 177. We think the mechanism of action is radiation leading to DNA damage. If there's enough radiation, then the cells can't repair themselves and die because of the radiation. The mechanism, I think, is radiation. There could be some other mechanisms, immune and other things, but I think the primary mechanism is radiation that is delivered to all of the PSMA-positive cells. Generally speaking, it's going to be most tumors in the advanced disease state will be PSMA-positive. Those small fractions that are negative are not included in the study. There is a screening PSMA-PET that is done that will eliminate those that have low or no PSMA expressions visible on the scans.

This transcript was AI generated and edited by human editors for clarity.