EXTRA-PC: a phase II trial of masofaniten (EPI-7386) and enzalutamide for patients with treatment-naïve metastatic hormone-sensitive prostate cancer.

[BACKGROUND] Anitens are a family of oral N-terminal domain inhibitors of the androgen receptor (AR). In prostate cancer, they may help overcome AR resistance mechanisms at the ligand-binding domain, which is the binding site of approved androgen receptor pathway inhibitors like enzalutamide. Masofaniten (EPI-7386) is a next-generation aniten with promising activity and safety in patients with metastatic castrate-resistant prostate cancer (mCRPC).

[METHODS] In this investigator-initiated, phase II, single-arm, single-institution trial, patients with treatment-naïve metastatic hormone-sensitive prostate cancer (mHSPC) were enrolled in a Simon 2-stage study design to receive the combination of masofaniten 600 mg BID and enzalutamide 160 mg daily with androgen deprivation therapy (ADT). The study was designed to enroll 35 patients (13 patients in stage 1, then 22 patients in stage 2). The trial would move to stage 2 if 9 or more subjects achieved a biochemical response at 6 months.

[RESULTS] Thirteen patients were screened and enrolled into stage 1. Five were African American, and 8 were Caucasian. The median age was 68 years (range 52-75) at time of enrollment. Median follow-up time was 9.9 months (range 7.7-13.6). Ten of 13 patients (77% with 95% CI: 50%-92%) achieved a PSA <0.2 ng/mL at 6 months, achieving the threshold to move on to stage 2. Only one patient had disease progression to mCRPC and died of disease at the time of data cutoff. Patients continued enzalutamide and ADT after trial closure.

[CONCLUSION] The combination of masofaniten and enzalutamide for treatment-naïve mHSPC did show efficacy and had an acceptable safety profile. These results support further investigation of the dual AR blockade in mHSPC (ClinicalTrials.gov Identifier: NCT06312670).