Phase 2 trial to evaluate NTD inhibitor in metastatic CRPC

Enrollment has commenced for the phase 2 portion of a phase 1/2 study (NCT05075577) exploring the investigational N-terminal domain (NTD) androgen receptor inhibitor masofaniten (formerly EPI-7386) in combination with enzalutamide (Xtandi) vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) naïve to second-generation antiandrogens.¹

Updated results from the phase 1 dose escalation portion of the trial are set to be presented during a session at the upcoming ESMO Congress in Madrid, Spain.

Masofaniten is an investigational, highly-selective, oral, small molecule inhibitor of the NTD of the androgen receptor. The agent was granted a Fast Track designation in 2020 for use in the treatment of adult male patients with mCRPC resistant to standard-of-care treatment.²

The current trial³ will assess the safety, tolerability, and preliminary efficacy of the combination of the NTD inhibitor with enzalutamide compared with that of enzalutamide alone. In total, the phase 2 dose expansion portion of the study is expected to enroll 120 patients with mCRPC.

Patients will be randomly assigned 2:1 to receive masofaniten/enzalutamide or enzalutamide monotherapy. The recommended phase 2 dose regimen based on findings from the phase 1 portion of the study was identified as 600 mg masofaniten twice daily combined with 160 mg enzalutamide once daily. The primary outcome measure is the proportion of patients with a prostate-specific antigen decline greater than 50% at 12-week follow-up.

Patients may remain on study treatment as long as they are tolerating treatment and experience no disease progression as defined by criteria from RECIST v1.1 and/or Prostate Cancer Clinical Trials Working Group 3.

Phase 1 of the trial was a single-arm study to assess the safety and tolerability of masofaniten in combination with enzalutamide. In total, the trial included 4 cohorts of patients (n = 80) that were given different treatment regimens to determine the recommended phase 2 dose.

Updated results from the phase 1 dose escalation portion of the trial are set to be presented during a session at the upcoming European Society of Medical Oncology Congress in Madrid, Spain.

"Initiation of the randomized Phase 2 portion of this study investigating the combination of masofaniten and enzalutamide (the "Combination") is a significant milestone for ESSA and we look forward to reporting updated results from the Phase 1 dose equilibration portion of the study next month at ESMO 2023," David Parkinson, MD, President and CEO of ESSA, said in a news release.¹

Parkinson added, "The favorable safety profile observed to date with the combination has led the safety review board to agree that we can proceed forward into the head-to-head comparison portion of the study with the dose regimen studied in Cohort 4 as our recommended phase 2 dose. We look forward to further elucidating the combination's potential to improve long-term clinical benefit for patients with mCRPC. We plan to provide guidance for timing of the public disclosure of initial data once the phase 2 portion has been underway for several months."

References

1. ESSA Pharma announces initiation of phase 2 study evaluating masofaniten (EPI-7386) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer. News release. ESSA Pharma Inc. September 18, 2023. Accessed September 19, 2023. https://www.prnewswire.com/news-releases/essa-pharma-announces-initiation-of-phase-2-study-evaluating-masofaniten-epi-7386-in-combination-with-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer-301929954.html

2. 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 19, 2023. https://bit.ly/3iCGsyL

3. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. EPI-7386 in combination with enzalutamide compared with enzalutamide alone in subjects with mCRPC. Last updated March 6, 2023. Accessed September 19, 2023. https://clinicaltrials.gov/study/NCT05075577