A Yale-led team says a new type of prostate cancer drug showed promising signs in men whose cancer had spread and stopped responding to standard hormone treatment. In an early trial, researchers reported falling levels of a blood marker for the cancer, shrinking tumors in soft tissue and less pain1. The results were published on October 9 in the Journal of Clinical Oncology1, and Yale School of Medicine announced them under the headline “Prostate Cancer Drug Shows Promise in New Clinical Trial”2.
The drug is called bavdegalutamide. It is the first drug of its kind, known as a PROTAC androgen receptor degrader, to be tested in patients1. The trial did not compare it with another treatment or a placebo (a dummy pill), so it cannot show how much of the change came from the drug itself.
What happened
The study was a combined phase 1 and phase 2 trial. Phase 1 is a first test of safety and dose in people; phase 2 starts to look at whether a drug has an effect1. In the first part, the researchers settled on a daily dose they found safe for patients who had already been treated for their advanced cancer1. In the second part, they looked at how patients responded1.
The main measure was PSA, short for prostate-specific antigen. PSA is a protein made by the prostate gland, and its level in the blood is often higher in men with prostate cancer3. The team measured it before and after patients took the drug1.
“There was a decrease in prostate-specific antigen. We also saw regressions in soft tissue lesions and improvements in pain,” says Petrylak. “These are the parameters that indicate a positive response.”
That quote is from Daniel Petrylak, a professor of medicine at Yale School of Medicine and senior author of the study1. “This is a first-in-class drug for prostate cancer,” he said1.
The researchers also looked at tumors with particular changes, called T878 and H875 mutations, in the receptor that responds to testosterone. In those cancers, PSA fell further1. The authors see this as a sign that drugs like this could be matched to patients based on their tumor’s genetics1.
Who the patients were
Everyone in the trial had been diagnosed with and treated for metastatic castration-resistant prostate cancer1. “Metastatic” means the cancer has spread beyond the prostate. When prostate cancer spreads, it often goes to the lymph nodes and to bones of the pelvis, ribs or spine, where it can cause pain3. “Castration-resistant” means the cancer keeps growing even when testosterone is kept very low1.
Doctors usually treat prostate cancer by starving it of testosterone, which stops its growth for a time1. In this form of the disease, that approach no longer holds it back. The form is incurable and lethal1. “More than 35,000 men will die from mCRPC in the United States this year,” Petrylak said1. A Yale Medicine fact sheet cites a National Cancer Institute estimate that around 35,800 men would die from prostate cancer overall in 20253. Prostate cancer is the most common cancer in men after skin cancer, and about one in eight men will be diagnosed with it in their lifetime3.
How the drug is meant to work
Cells constantly break down old proteins and recycle the parts. This process is called proteolysis. PROTACs are a new class of cancer drug that try to use that natural system to get rid of proteins that help cancer grow1.
Bavdegalutamide targets the androgen receptor, the part of the cell that responds to testosterone and drives prostate cancer growth1. Instead of lowering testosterone or blocking the receptor, it is designed to have the receptor destroyed, as a way around the resistance these cancers build to other hormone treatments1.
“Bavdegalutamide takes your own natural protein degradation system, and it accelerates the process for the androgen receptor. The drug degrades the receptors for testosterone, which control prostate cancer growth,” says Petrylak.
The idea came out of Yale. PROTACs were pioneered by Yale researcher Craig Crews, whose work also led to the first PROTAC approved by the U.S. Food and Drug Administration, a breast cancer drug1.
What it does not show yet
This was an early trial. The summaries available to Biohack do not give the number of patients, how many saw their PSA fall, by how much, or how long any response lasted. They also do not describe side effects beyond saying the chosen dose was found safe in the first part of the study1.
The trial did not include a comparison group. Without one, it is hard to tell how much of the change in PSA, tumor size or pain came from the drug and how much would have happened anyway or because of other care. PSA is a marker in the blood, not a direct measure of whether men live longer or feel better over time. The sources do not report survival results.
The finding about tumors with specific receptor mutations comes from smaller subgroups within the trial. Results like that usually need to be checked in larger studies before doctors rely on them to choose treatment.
Who is behind it
The study was led from Yale. Its first author is Xin Gao, and Petrylak, a member of Yale Cancer Center, is the senior author1. The report on Medical Xpress was provided by Yale School of Medicine, so it reflects the university’s own account of the work1. The sources read for this article do not say who paid for the trial or whether any authors have ties to a company developing the drug.
What to watch next
The same researchers are now testing a second drug of this kind, called ARV 766, in combined phase 1 and phase 2 trials1. It is reported to work against a wider range of androgen receptor mutations than the earlier drug, ARV-1101.
Things to look for next:
- Fuller numbers from the published paper: how many men responded and for how long.
- Any larger trial that compares a drug of this class with existing treatment.
- Early results from the second drug, ARV 7661.
- Whether testing tumors for specific receptor mutations becomes part of choosing who gets these drugs1.
For now, the findings come from an early, uncontrolled trial. They show that men taking the drug had lower PSA, some tumor shrinkage and less pain, as the researchers reported, but not how much of that the drug itself caused.
