ESSA Pharma has discontinued its phase 2 study evaluating the combination of masofaniten (EPI-7386), a novel androgen receptor inhibitor, and enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC). The decision, announced on October 31, 2024, was prompted by a futility analysis indicating a low probability of achieving the primary endpoint: a prostate-specific antigen (PSA) response of at least 90% (PSA90).
The open-label, randomized phase 2 trial (NCT05075577) enrolled adult patients with mCRPC who had not previously received second-generation antiandrogens. Participants were recruited from sites in the United States, Canada, Australia, and France. The study aimed to enroll approximately 120 patients, with a 2:1 randomization to either the combination arm (masofaniten 600 mg twice daily plus enzalutamide 160 mg daily) or the enzalutamide monotherapy arm (160 mg daily).
Interim Efficacy Results
The interim efficacy analysis included data from 52 patients with at least one PSA measurement post-baseline and 41 patients with a minimum of three months of follow-up. Results showed that the PSA90 response rate was 64% in the masofaniten plus enzalutamide arm compared to 73% in the enzalutamide monotherapy arm. The proportions of patients achieving a PSA response of at least 50% (PSA50) were 88% and 87%, respectively.
At 90 days, the PSA50 response rates were 93% in the combination arm and 86% in the monotherapy arm, while the 90-day PSA90 response rates were 67% and 71%, respectively. These findings led ESSA Pharma's senior management and board of directors to conclude that the combination therapy was unlikely to demonstrate a significant clinical benefit over enzalutamide alone.
Safety and Tolerability
According to the news release, the combination of masofaniten and enzalutamide was generally well-tolerated, and no new safety signals were identified during the study. Masofaniten had previously received fast track designation from the FDA in September 2020 for mCRPC patients resistant to standard-of-care therapies.
Leadership Perspective
"Providing a meaningful clinical benefit to patients in our clinical trials, along with a robust safety profile, is of utmost importance to us at ESSA," stated David Parkinson, MD, president and chief executive officer of ESSA. "We designed this randomized study to rigorously evaluate the clinical benefit of adding masofaniten to enzalutamide. We made the difficult decision to terminate this phase 2 study following the interim analysis because we concluded that the emerging efficacy profile of masofaniten combined with enzalutamide would not likely meet the primary end point of the study, nor our internal requirements for a prostate cancer therapy candidate."
Study Design
Key eligibility criteria for the trial included evidence of disease progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, an ECOG performance status of 0 or 1, ongoing androgen deprivation therapy, and adequate organ function. The primary endpoint was the PSA90 response rate, with secondary endpoints including PSA50 response rate, 12-week PSA50 and PSA90 response rates, and time-to-event outcomes. However, the time-to-event outcomes were not mature at the time of the interim analysis.
Patients remained on the study as long as the treatment was tolerable and there was no disease progression per RECIST 1.1 and/or PCWG3 criteria. ESSA Pharma retains all global rights to masofaniten.
