ARV-110 On the Horizon

The Food and Drug Administration (FDA) has approved a new Phase 1 clinical trial to evaluate ARV-110 for men with metastatic castration-resistant prostate cancer (mCRPC).

The trial, which should begin by April 2019, will investigate the safety and tolerability of ARV-110 in men with mCRPC whose cancer has progressed after being treated with and failed at least two standard of care therapies.

Currently approved drugs like Zytiga (abiraterone) and Xtandi (enzalutamide) target the androgen receptor (AR).  However, over time the cancer tumors develop resistance to these drugs.  Current thought is that this resistance develops when the cancer cells overproduce the androgen receptor or when the cells produce a variant of the androgen receptor, called AR-V7.  

It is believed that degrading this AR might be a promising approach for treating these progressed types of prostate cancers.  A company called Arvinas has developed a protein degradation platform (ARV-110) which tags prostate cancer-causing proteins for degradation.

This ARV-110 delivers small molecules to the androgen receptor that function as flags for the cells’ natural protein degrading system leading to the degradation of the AR.

In preclinical studies, ARV-110 reduced androgen receptor levels by 95-98% in several prostate cancer cell lines. Additionally, in a mouse model of prostate cancer, ARV-110 inhibited tumor growth by up to 100%.

While these cancer cells had not yet been exposed to androgen receptor inhibitors, a study in mice implanted with prostate cancer cells from a patient with acquired resistance to Xtandi, also showed that ARV-110 reduced tumor growth by up to 70%.

Cancer ABCs believes that this investigation treatment warrants our following it as it progresses through its Phase 1 trial and then hopefully into and through a phase 3 trial.