Recruiting at sites in Arizona and South Carolina, the open-label trial (NCT04575766) is expected to enroll 45 patients who failed to respond to at least one potent anti-androgen treatment. Contact and site information can be found here.
“Initiating enrollment in this Phase 1 trial is an important step toward our goal of providing mCRPC patients with an additional therapeutic option to treat this severe illness,” David Cook, PhD, chief scientific officer of Forma, said in a press release.
Hormone therapies targeting male sex hormones, or androgens, are a mainstay in treating prostate cancer. Androgens bind to the androgen receptor, activating signals that prostate cancer cells require to grow and proliferate.
However, patients often develop mutations in the androgen receptor that render it resistant to such therapies over time. New treatments that block androgen signaling through distinct mechanisms may help men whose cancer is no longer responding to standard hormone therapies.
“While a patient with mCRPC may initially respond to standard anti-androgen therapies, a significant unmet need persists since nearly all patients ultimately become resistant to these treatments,” said Cook.
One of the mechanisms linked with resistance is the production of a variant of the androgen receptor, called AR-V7, that is able to escape the action of androgen receptor inhibitors. In other cases, cancer cells overproduce the androgen receptor.
FT-7051 is designed to selectively inhibit the CBP/p300 complex, an activator of the androgen receptor that is required for tumor growth even in cancers that no longer respond to current androgen-targeted treatments.
Studies in prostate cancer cell lines showed that FT-7051 lowers the production of the androgen receptor, as well as its activation — as measured by the expression of genes dependent on androgen receptor signaling.
The therapy also lessened cancer growth, including in cells producing the AR-V7 resistant variant.
The ongoing trial is investigating the safety, tolerability, pharmacokinetics and pharmacodynamics (how a treatment moves through the body and how it affects the body) of FT-7051 in mCRPC patients who have failed at least one anti-androgen therapy.
Those enrolled will receive one of seven ascending doses of FT-7051, starting at a 25 mg dose, taken as oral capsules once daily for the first 21 days of each four-week cycle. The goal is to determine the most effective and safest dose for further trials.
The study’s primary goal is the safety and tolerability of FT-7051, by monitoring dose-limiting toxicities in the first four weeks, and treatment-related adverse events and abnormalities in lab results for up to 26 weeks.
Researchers will also be looking for preliminary signs of efficacy, measuring the anti-tumor activity of FT-7051 through prostate-specific antigen (PSA) levels, a marker of this cancer, and radiographic responses.