A first patient has been dosed in a Phase 1 clinical trial investigating the small molecule inhibitor EPI-7386 as a treatment for metastatic castration-resistant prostate cancer (CRPC), its developer, ESSA Pharma, reported.
Metastatic CRPC is prostate cancer that has metastasized, or spread to distant regions, and is resistant to traditional treatments that lower levels of androgen hormones, like testosterone.
Recruitment for this open-label trial (NCT04421222) testing four doses of the oral candidate, is underway at three U.S. sites: the Hematology Oncology Associates of the Treasure Coast in Florida, the Comprehensive Cancer Center of NV Las Vegas in Nevada, and at Washington University School of Medicine in Missouri.
Additional testing sites in Florida and British Columbia are expected to open soon. Information is available here.
“The initiation of this study represents a significant milestone for ESSA as it brings us a step closer to offering a potentially meaningful new therapeutic option to prostate cancer patients,” David Parkinson, MD, CEO of ESSA, said in a press release.
Research indicates that prostate cancer requires the presence of androgens in order to grow. For this reason, lowering androgen levels through surgery or hormone therapy is a mainstay of its treatment.
When patients become resistant to these therapies, however, those that block the androgen receptor (AR) take the center stage. Several androgen receptor inhibitors — Zytiga (abiraterone acetate), Xtandi (enzalutamide), Erleada (apalutamide) — are now approved to treat prostate cancer.
Still, many patients will develop resistance to both androgen lowering therapies and those blocking androgen signaling. Resistance often develops because the AR protein acquires mutations in its active site that renders these treatments ineffective.
Research, for this reason, has turned to approaches that target AR in a different region: its N-terminal (the initial portion of a protein).
EPI-7386 is an investigational small molecule that inhibits AR signaling by binding to this region of the receptor, potentially stoping the growth of cancers resistant to other forms of anti-androgen therapy.
Preclinical studies showed that EPI-7386 was active in models of prostate cancer that were either sensitive or resistant to androgen receptor inhibitor treatments, prompting.
The Phase 1 clinical trial expects to enroll 28 metastatic CRPC patients who failed to respond to standard anti-androgen treatments, including the more advanced androgen receptor inhibitors.
It aims to investigate the safety, tolerability, pharmacokinetics (how a drug moves through the body), and anti-tumor effects of oral EPI-7386 taken daily, over five months.
In a first part, 18 patients will be randomized for 28 treatment days to one of five increasing doses of EPI-7386 — 200 mg, 400 mg, 600 mg, 800 mg, and 1,000 mg — to help establish an optimal dose or until a dose-limiting toxicity, or the dose at which serious side effects prevent further increases, is reached.
Its second part will add 10 more patients, and monitor participants’ blood for evidence of a 50% decrease in the levels of the protein prostate-specific antigen (PSA), a common biomarker for prostate cancer, while on treatment.
That drop in PSA blood levels will serve as the trial’s primary measure of early efficacy for EPI-7386.
“The fact that EPI-7386 was first synthesized less than two years ago and yesterday began dosing in patients is a testament to the efficiency of our team and our collaborators,” Parkinson said. “The results from this trial will guide our future development plans and confirm the potential contribution of N-terminal domain AR inhibition to the treatment of prostate cancer.”