ESSA Pharma has announced the termination of its Phase 2 clinical trial (NCT05075577) evaluating the combination of masofaniten (formerly EPI-7386) and enzalutamide (Xtandi) versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). The decision follows a pre-specified futility analysis that indicated the combination therapy was unlikely to meet its primary endpoint.
The interim analysis revealed that 64% of patients in the combination arm achieved a PSA90 response (≥90% decline in prostate-specific antigen), compared to 73% in the enzalutamide monotherapy arm. David Parkinson, MD, president and CEO of ESSA, stated that the emerging efficacy profile of masofaniten combined with enzalutamide would not likely meet the study's primary endpoint, nor ESSA's internal requirements for a prostate cancer therapy candidate.
Trial Details and Findings
The open-label Phase 2 trial aimed to enroll 120 adult patients with mCRPC, randomizing them in a 2:1 ratio to receive either 600 mg of masofaniten twice daily plus 160 mg of enzalutamide once daily, or 160 mg of enzalutamide monotherapy once daily. The interim analysis included data from 52 patients who had at least one PSA measurement after baseline, with 41 patients completing at least three months of follow-up.
Secondary endpoints included the proportion of patients achieving a PSA50 response (≥50% decline in PSA) and the PSA50 and PSA90 response rates at 90 days. At the time of data report, 88% of patients in the combination arm and 87% in the monotherapy arm achieved a PSA50 response. At 90-day follow-up, the PSA50 response rate was 93% in the combination arm compared to 86% in the monotherapy arm, while the PSA90 response rate was 67% and 71%, respectively.
The combination therapy was reported to be well-tolerated, with no new safety signals identified.
Impact on Further Development
ESSA Pharma also plans to terminate other ongoing clinical trials evaluating masofaniten, both as a monotherapy and in combination with other agents, including a study assessing masofaniten in combination with abiraterone acetate (Zytiga) or apalutamide (Erleada) (NCT05295927).
Patient Eligibility
Patients eligible for the trial were those who had not previously been treated with second-generation anti-androgens, had an ECOG performance score of 0 or 1, a serum testosterone level of 1.73 nmol/L (50 ng/dL) or less, and demonstrated adequate organ function. The trial enrolled patients at clinical trial sites in the United States, Canada, Australia, and France.
Masofaniten had previously received Fast Track designation from the FDA in September 2020 for the treatment of mCRPC patients resistant to standard-of-care therapies.
