At Perlmutter Cancer Center, clinical trials are testing the mettle of two new classes of medications designed to rein in aggressive prostate cancers.

Lutetium-177-PSMA-617 is an experimental therapy that targets a cancer cell protein called prostate-specific membrane antigen, or PSMA, that is prevalent in people with metastatic disease. The compound is coupled with a radioactive particle designed to destroy malignant cells. It’s a precision-guided approach that Dr. David R. Wise likens to a smart bomb. Early studies showed that the therapy can delay disease progression among patients by 60 percent.

Up next, NYU Langone researchers will begin enrolling patients in a phase 3 trial in fall 2021. If all goes well, the drug could receive U.S. Food and Drug Administration (FDA) approval next year.

A second clinical trial looks at using DKN-01 to treat prostate cancer. In a paper published in JCO Precision Oncology, Dr. Wise reported that as prostate cancers become more aggressive, they become less dependent on testosterone, which is why the suppression of male hormones often fails. Instead, the cancer cells activate a gene called DKK1 that fuels their growth. Leveraging that knowledge, Perlmutter Cancer Center is testing DKN-01, a monoclonal antibody designed to inhibit the DKK1 protein. The trial is funded in part by the Prostate Cancer Foundation and the biotech company Leap Therapeutics, for which Dr. Wise is a paid consultant.

The trial evaluates the effectiveness of the monoclonal antibody—both alone and in combination with chemotherapy—at triggering the immune system to identify and attack cancer cells. “This treatment is not going to be for every patient whose metastatic cancer is resistant to hormone therapy,” Dr. Wise says, “but we think 25 percent to 30 percent of these men may benefit, which would be a significant and exciting development for our field.”

Study results are expected to be published in winter 2021.