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Combo of novel NTD inhibitor plus darolutamide explored in mCRPC


A phase 1/2 trial is launching to explore the combination of the investigational NTD androgen receptor inhibitor EPI-7386 and darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer (mCRPC).1

The study will examine the efficacy, safety, and pharmacokinetics of the combination. The official launch is anticipated this year, according to ESSA Pharma Inc., the developer of EPI-7386.

"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. R. Parkinson, MD, CEO, ESSA, stated in a press release.

"EPI-7386 binds to the androgen receptor targeting the opposite end of the androgen receptor from current therapies. In preclinical models, we have seen that combining EPI-7386 with current antiandrogens 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," added Parkinson.

The small molecule inhibitor previously demonstrated preclinical activity in models of antiandrogen-sensitive and -resistant prostate cancer. An ongoing phase 1 trial (NCT04421222) is now assessing the safety and tolerability of single-agent EPI-7386 in patients with mCRPC who progressed on standard therapies, including second-generation antiandrogens.2

In September 2020, it was announced that the FDA had granted a Fast Track Designation to EPI-7386 for the treatment of patients with mCRPC resistant to standard-of-care treatments.3 In an interview with Urology Times at the time of the designation, J. Brantley Thrasher, MD, explained that EPI-7386 is part of a new class of AR-targeting compounds known as anitens.

“These compounds differ from currently available AR-blocking compounds because they bind to the N-terminal domain of the AR instead of the ligand binding domain. Due to its novel binding and mechanism of blocking the AR, it appears to work well in those patients who are progressing on current standard of care treatments,” said Thrasher, executive director of the American Board of Urology in Charlottesville, Virginia.

Added Thrasher, “I think this therapy will provide another agent in the armamentarium for mCRPC and will likely be used at first for those recalcitrant to standard therapies like enzalutamide [Xtandi] or abiraterone [Zytiga] but will quickly be tested to find out whether it works best in combination with one of these agents and what the best sequence of delivery will be.”

Along that line, EPI-7386 is also currently being explored in combination trials with other antiandrogen agents, including apalutamide (Erleada), abiraterone acetate, and enzalutamide, through partnerships set up by ESSA.


1. ESSA Pharma Announces Clinical Collaboration Agreement with Bayer to Evaluate the Combination of EPI-7386 and Darolutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. Published on April 28, 2021. Accessed April 28, 2021. https://prn.to/3vszbI4.

2. ESSA Pharma announces fast track designation granted by the FDA to EPI-7386 for the treatment of metastatic castration-resistant prostate cancer. Press release. Essa Pharma. September 14, 2020. Accessed Sept. 16, 2020. https://bit.ly/3iCGsyL.

3. 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.

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