Zenith Epigenetics has started a Phase 1b clinical trial to assess the safety and tolerability of its orally administered BET inhibitor ZEN-3694 in combination with Xtandi (enzalutamide) in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed after first-line androgen-deprivation therapy.
Current standard of care treatment for prostate cancer patients consists of androgen deprivation therapies such as Xtandi, which blocks the androgen receptor, or Zitiga (abiraterone), which impairs the synthesis of androgens. Although most patients respond to these castration therapies, nearly all patients eventually become resistant to them.
Castration-resistant prostate cancer patients have no effective therapies to treat their disease. But recently, pre-clinical studies have suggested that BET inhibitors, which disrupt DNA remodeling and gene expression, leading to the inhibition of cancer cell proliferation, show promise in mCRPC patients.
The open-label, single-arm study (NCT02711956) will assess the safety and tolerability of the BET inhibitor ZEN-3694 in combination with Xtandi in mCRPC patients. It will encompass a first dose-escalation phase to assess the optimal ZEN-3694 dose and dose-limiting toxicities, followed by an expansion phase assessing the safety of ZEN-3694 at the selected dose.
“We are excited to reach this second important milestone for Zenith Epigenetics and the development of ZEN-3694,” Donald McCaffrey, president and CEO of Zenith, said in a news release. “There remains a significant unmet need and poor prognosis for mCRPC patients who have progressed on anti-androgen therapies.
“Recognizing the importance of combination treatment for bromodomain (BET) inhibitors for these patients places Zenith Epigenetics at the forefront of development of these novel epigenetic drugs for the treatment of metastatic castration resistant prostate cancer,” he added.
The study is slated to enroll up to 58 metastatic castration-resistant prostate cancer patients who progressed on Zytiga (abiraterone) therapy or who are currently taking Xtandi but experienced PSA progression. Participants will receive oral ZEN-3694 once daily with Xtandi in 28-day cycles.
The study’s primary outcomes are the incidence of dose-limiting toxicities or treatment-related adverse events. Secondary outcomes include several drug property parameters, as well as PSA and radiographic response, median progression-free survival, and circulating tumor cell response rate.
Measures of the drug’s properties include average, peak, and minimum plasma concentration, time from administration of the dose to maximum concentration, and the half-life of the drug. These will be taken on days 1, 2, and 15 over eight different time intervals.
The trial is already recruiting participants in California and New York, and will soon be recruiting in Michigan, Oregon, and Virginia. For more information on patient eligibility and study locations, visit the clinical trial site.