Targeting PSMA in mCRPC With Novel Antibody-Drug Conjugate 225Ac-J591

John T. Nauseef, MD, PhD, assistant professor of medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, and assistant attending physician at NewYork-Presbyterian Hospital, discusses an investigational prostate-specific membrane antigen (PSMA) targeted therapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

In a phase 1 study for which data were presented at the American Society for Cancer Research (AACR) Annual Meeting 2023, the drug, 225Ac-J591 was shown to induce preliminary efficacy and few high-grade adverse events occurred.

Transcript:

0:08 | There are a couple different ways to target PSMA. One is with a small molecule ligand, and the other one would be with a monoclonal antibody. So, J591 is our monoclonal antibody that has terrific targeting on cells that are expressing PSMA, and it helps with internalization into the cell. This monoclonal antibody is going to go throughout the body and with it carry actinium 225, and that is a very potent radionuclide. So, with the antibody going to the sites where you want it to go, it will bring with its payload, which is radionuclide.

0:46 | This is important. You know, patients with mCRPC can have cancer anywhere in their body, and you want to be able to target this. You can do that effectively with an antibody like J591 and bring with it a very potent radionuclide. That’s one of the things that's so nice about the potency of this drug is that it has a very short path length. So, though you're delivering a high energy that even a single hit on a cell can result in double stranded DNA breaks and cell death, the path length is very short. So, your toxicity potentially may be lower because the drug isn't going to get away from where you want it to be. This will be true anywhere that a patient has cancer that can be commonly in the bones, the lymph nodes, but also visceral sites of disease, such as the liver and lungs.