The preliminary results of a Phase I clinical trial conducted by researchers at the Yale Cancer Center (YCC) have shown that ARV-110, an androgen receptor PROTAC® protein degrader, demonstrates clinical evidence of anti-tumor responses in patients with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior therapy. While most drugs target the androgen receptor by either reducing testosterone or blocking its binding to the androgen receptor, ARV-110 is unique in that exploits a normal cellular pathway to overcome resistance to antiandrogen treatments. The findings from this study are to be shared in an oral presentation at the virtual Scientific Program at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting on May 29.
Led by Daniel Petrylak, M.D., professor of Medicine and Urology at YCC and Disease Aligned Research Team Leader for the Prostate and Urologic Cancers Program at Smilow Cancer Hospital, the clinical trial was conducted across four centers and evaluated 22 patients who had previously received at least two systemic therapies and had progression of disease through an increasing level of prostate specific antigen (PSA) or additional metastatic lesions. Of these 22 patients, seven were treated at dose levels predicted by preclinical studies to be therapeutic and had forms of androgen receptors that ARV-110 would be expected to degrade. Two of the seven patients were confirmed to experience a greater than 50 percent decrease in their PSA level, and one of these two patients demonstrated a greater than 50 percent reduction in tumor size.
In 2020, metastatic castration-resistant prostate cancer is estimated to account for approximately 39,000 deaths, according to the International Journal of Molecular Sciences. While androgen deprivation therapy is the initial treatment for hormone sensitive metastatic prostate cancer, despite rapid and dramatic responses, nearly all patients progress to mCRPC.
“We are extremely pleased with the current results of this first-in-class, first-in-human Phase I study and anticipate expansion to a Phase II trial once we establish a recommended dose,” said Dr. Petrylak. “This is a potential new option that approaches treating metastatic castration-resistant prostate cancer in a completely different way.”
The study was funded by Arvinas.