FDA Grants Fast Track Status to EPI-7386 in mCRPC

The FDA granted a fast track designation to the highly-selective N-terminal domain inhibitor EPI-7386 for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who are resistant to standard-of-care options, according to an announcement from ESSA Pharma Inc.¹

“We are pleased with the FDA’s decision to grant fast track designation for development of EPI-7386 to treat [patients with] mCRPC resistant to standard-of-care treatments,” David R. Parkinson, MD, chief executive officer of ESSA Pharma, stated in a press release. “This designation signifies recognition of the unmet medical need for new and effective treatments for this patient population. EPI-7386 may represent a promising novel treatment option for these patients and the designation offers the opportunity to interact more closely with the FDA during the development [of the agent].”

Previously, the small molecule inhibitor demonstrated preclinical activity in models of antiandrogen-sensitive and -resistant prostate cancer. Now, the safety and tolerability of EPI-7386 in patients with mCRPC who progressed on standard therapies, including second-generation antiandrogens, is under examination in a phase 1 trial (NCT04421222).

As this is a first-in-human trial, the main goal is to examine the safety of the agent and to identify a dose that can be administered to this patient population without any intolerable adverse effects (AEs).² Other key factors that will be examined include how the amount of the drug in the blood changes over time, the effect of the agent on the disease, the impact of the drug on certain substances in the body, and the possibility of EPI-7386 being able to interact with other agents.

To be eligible for participation, patients had to be 18 years of older; have histologically, pathologically, or cytologically confirmed prostate cancer without small cell features; evidence of castration-resistant disease; metastatic disease upon study entry as documented by 1 or more bone lesions or soft tissue disease; and evidence of progressive disease. Additionally, patients had to have recovered from AEs associated with previous therapies, have acceptable organ function, and an ECOG performance status of 0 to 1.

If patients had received biologic anticancer treatment, cytotoxic chemotherapy, or hormonal agents within 4 weeks before treatment with the study drug; if they received treatment with radium-223 dichloride (Xofigo) or another radiopharmaceutical within 28 days before treatment with the drug; and if they had a blood transfusion within 28 days of screening, they were not permitted for inclusion.

The dosing of the first patient on the phase 1 trial was announced by the clinical-stage pharmaceutical company on July 15, 2020.³ “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 [patients with] prostate cancer,” Parkinson commented in an earlier press release. The fact that EPI-7386 was first synthesized less than 2 years ago and began dosing in patients is a testament to the efficiency of our team and our collaborators.”

The phase 1 trial is anticipated to enroll approximately 18 patients with mCRPC for the dose-escalation phase, which will be conducted at several clinical sites in the United States and Canada. Investigators plan to enroll 10 additional patients for the dose-expansion cohort, which will involve more clinical sites.

Beyond determining the safety and tolerability of EPI-7386, investigators are also focused on learning more about the pharmacokinetic, biologic, and antitumor effects of the agent in this patient population.

References

1. ESSA Pharma announces fast track designation granted by the FDA to EPI-7386 for the treatment of metastatic castration-resistant prostate cancer. News release. ESSA Pharma Inc. September 14, 2020. Accessed September 14, 2020. https://prn.to/3ivyszv.
2. Oral EPI-7386 in patients with metastatic castration-resistant prostate cancer (EPI-7386). ClinicalTrials.gov. Updated July 29, 2020. Accessed September 14, 2020. https://clinicaltrials.gov/ct2/show/NCT04421222.
3. ESSA Pharma announces first patient dosed in a phase 1 clinical trial of EPI-7386 for metastatic castration-resistant prostate cancer. News release. ESSA Pharma Inc. July 15, 2020. Accessed September 14, 2020. https://bit.ly/2FkdHbZ.