VIDEO: Proteolysis-targeting chimeras show promising results in prostate cancer

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So approximately 20 to 25% of men with metastatic castration-resistant prostate cancer ultimately develop mutations in what's called the AR binding domain. Among these, there's three in particular, L702H, H875Y, and T878A that are the most common and typically associated with a poor prognosis. So ARV-766, it's what's called a proteolysis-targeting chimera or a PROTAC, and it targets the wild-type AR, and it's very clinically relevant for these ligand binding domain mutants.

Unlike the androgen receptor pathway inhibitors that we're all very familiar with, the Zytigas, XTANDIs, and Erleada of the world, PROTACs have been shown to exert what's called a bystander effect, meaning that it can target neighboring proteins within the protein complex. At ASCO this year, there is a phase one/two study reported out by Dr. Dan Petrylak which is the first data we saw out of a dose escalation study looking at two doses, 100 and 300 milligrams. It was open to all comers, and then the study sort of narrowed down to those ligand binding domain mutants we just discussed.

So in those early results, we saw some really encouraging numbers. So PSA 30 was 51%, PSA 50 was 43%, and the overall response rate was 30% with the swimmers to plot depicting about 25% of patients reaching about six months or more on therapy. In this patient population, that is quite impressive because these are heavily pretreated patients on several lines of therapy prior to this treatment, so I think it does represent a potential novel targeted strategy that may be in the pipeline in the months to years to come.