ARV-766 for Patients With Metastatic Castration-Resistant Prostate Cancer Harboring Androgen Receptor LBD Mutations
At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Daniel Petrylak, MD, Smilow Cancer Center, Yale School of Medicine, New Haven, Connecticut, discussed results from a phase 1/2 study that demonstrated that ARV-766 was well tolerated and showed promising clinical activity among patients with androgen receptor LBD-mutated metastatic castration-resistant prostate cancer (mCRPc).
Transcript:
My name is Daniel Petrylak, I'm a professor of medicine and urology at the Smilow Cancer Center, Yale University.
Ubiquitination of proteins is a way that our body disperses the proteins and turns over both mutated as well as wild-type proteins, PROTACs are drugs that will accelerate this particular process. Initially, we started work with a drug called ARV-110 which demonstrated activity in castrate-resistant prostate cancer, but did have significant nausea and fatigue. ARV-766 is a second-generation compound that has a broader range of activity, it recognizes more mutations in the ligand binding domain, as well as in the wild-type, and helps to degrade the androgen receptor. Approximately, 1 ARV-766 molecule can take out 400 copies of the androgen receptor. In this study, we took men with castration-resistant prostate cancer and those patients who had ligand binding domain mutations. We found that 30% of patients with measurable soft tissue lesions had a RESIST response. This was also coupled with 43% of patients having at least a 50% PSA decline. From this study, we concluded that ARV-766 is active in castration-resistant prostate cancer and warrants further evaluation.
Source:
Petrylak DP, ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract 5011
