Patients with mCRPC will be randomly assigned 2:1 to receive masofaniten/enzalutamide or enzalutamide alone.
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
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."
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