Essa Pharma has entered a clinical collaboration with Janssen to evaluate its small molecule inhibitor EPI-7386, in combination with either Erleada (apalutamide) or Zytiga (abiraterone acetate) plus prednisone, for patients with metastatic castration-resistant prostate cancer (mCRPC).
Under the terms of the agreement, Janssen will conduct up to two Phase 1/2 clinical trials evaluating these combinations in people who failed second-generation androgen receptor inhibitors such as Erleada or Zytiga.
A joint committee from both companies will oversee the trials, which are expected to begin this year. Janssen will support all costs, while Essa will ensure the clinical supply of EPI-7386 for the trials.
“We are delighted to collaborate with Janssen to explore the potential clinical role of EPI-7386 in combination with the antiandrogens apalutamide and abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer,” David Parkinson, MD, president and CEO of ESSA Pharma, said in a press release.
A number of androgen receptor inhibitors — Zytiga, Erleada, and Xtandi (enzalutamide) — are approved for patients who acquired resistance to hormone therapies, which lower the levels of androgens, the male sex hormones that drive prostate cancer.
Still, many patients also stop responding to these treatments, often due to mutations in the androgen receptor gene that renders those treatments ineffective.
Essa Pharma’s EPI-7386 works differently from current androgen receptor inhibitors, by targeting a different region of that receptor. Rather than preventing androgens from binding the receptor, the candidate therapy binds to the N-terminal domain (the initial portion of a protein), which is needed to activate the androgen signaling cascade.
This suggests that EPI-7386 might be effective not only in prostate cancer patients who no longer respond to androgen receptor inhibitor treatments, but also in those who are still sensitive to such treatments.
“In preclinical models, we have seen that combining EPI-7386 with current anti-androgens can lead to deeper and broader inhibition of androgen biology. We look forward to investigating these combination therapies and their potential to improve the treatment of prostate cancer,” Parkinson added.
An ongoing open-label Phase 1 trial (NCT04421222) is evaluating the safety, tolerability, and preliminary signs of efficacy of EPI-7386 alone, taken as a daily pill for five months.
The trial intends to recruit 40 adults with mCRPC who failed to respond to standard anti-androgen treatments. Enrollment is ongoing at four clinical sites in the U.S. and Canada.
In a first part, participants will receive one of five doses of EPI-7386 — ranging from 200 to 1,000 mg — for four weeks, to help establish an optimal dose for future trials.
A second group of patients then will receive the treatment at the established dose to investigate its efficacy. The main goal in this part is to determine the proportion of patients who experience a 50% or greater decline in their prostate-specific antigen levels, which would represent a meaningful reduction in tumor burden.