Phase 2 trial of masofaniten plus enzalutamide in mCRPC has been terminated

ESSA Pharma has terminated a phase 2 trial (NCT05075577) exploring the combination of masofaniten (formerly EPI-7386) and enzalutamide (Xtandi) vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC), the company announced in a news release.¹

At the time of data report, 64% of patients in the combination arm vs 73% of patients in the monotherapy arm achieved a PSA90 response.

The decision comes after a pre-specified futility analysis determined that the safety, pharmakinetic, and efficacy of single-agent enzalutamide performed better than historical controls and comparable to the combination arm. Based on this interim analysis, it was determined to be unlikely that the study would meet its primary end point.

The company also plans to terminate other remaining clinical trials evaluating masofaniten as either a monotherapy or in combination with other agents. This includes a study assessing masofaniten in combination with abieraterone acetate (Zytiga) or apalutamide (Erleada) (NCT05295927).

"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," said David Parkinson, MD, president and CEO of ESSA, in the news release.¹ "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. We would like to thank our partners, investigators, employees, and most importantly, the patients and their families involved in our clinical trials."

Specifically, at the time of data report, 64% of patients who completed at least 1 month of treatment in the combination arm vs 73% of patients in the enzalutamide monotherapy arm achieved the study’s primary end point of at least a 90% prostate-specific antigen (PSA) decline (PSA90 response). Regarding the study’s secondary end points, 88% of patients in the combination arm vs 87% of patients in the enzalutamide monotherapy arm achieved a at least a 50% decline in PSA (PSA50).

At 90-day follow-up, the PSA50 response rate was 93% in the combination arm compared with 86% in the monotherapy arm. Additionally, the PSA90 response rate was 67% in the combination arm and 71% in the monotherapy arm.

Regarding safety, the combination was well-tolerated, with no new safety signals emerging.

In total, the open-label phase 2 trial planned to enroll 120 adult patients with mCRPC who would be randomly assigned 2:1 to received 600 mg masofaniten BID plus 160 mg enzalutamide QD or to 160 mg enzalutamide monotherapy QD. The interim analysis, which prompted termination of the trial, included 52 of the planned 120 patients (48%) who had at least 1 PSA measurement after baseline. Of those, 41 patients completed at least 3 months of follow-up.

Patients were eligible for enrollment in the trial if they were naïve to second generation anti-androgens, had an ECOG performance score of 0 or 1, had a serum testosterone of 1.73 nmol/L (50 ng/dL) or less, and demonstrated adequate organ function.² Patients were enrolled throughout clinical trial sites in the United States, Canada, Australia, and France.

The primary end point for the study was the proportion of patients who achieved a PSA90 response. Secondary end points included the proportion of patients achieving a PSA50 response as well as the PSA50 and PSA90 response rates at 90 days.

Data from the phase 1 portion of the trial were previously presented at the 2023 European Society for Medical Oncology Annual Congress.³ Overall, data showed that the combination of masofaniten plus enzalutamide was well tolerated and elicited durable reductions in PSA levels in patients with mCRPC.

Masofaniten was granted a fast track designation by the FDA in September 2020 for development in patients with mCRPC who are resistant to standard of care therapies.⁴

References

1. ESSA Pharma announces termination of phase 2 study evaluating masofaniten combined with enzalutamide in patients with metastatic castration-resistant prostate cancer. News release. ESSA Pharma Inc. October 31, 2024. Accessed November 1, 2024. https://investors.essapharma.com/2024-10-31-ESSA-Pharma-Announces-Termination-of-Phase-2-Study-Evaluating-Masofaniten-Combined-with-Enzalutamide-in-Patients-with-Metastatic-Castration-Resistant-Prostate-Cancer

2. EPI-7386 in combination with enzalutamide compared with enzalutamide alone in subjects with mCRPC. ClinicalTrials.gov. August 28, 2024. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT05075577

3. Phase I/II trial of oral EPI-7386 in combination with enzalutamide (enz) compared to enz alone in metastic castration-resistant prostate cancer (mCRPC) subjects: Current phase I (PI) results. Presented at the European Society of Medical Oncology (ESMO) Congress. October 26-28, 2023. Madrid, Spain. Abstract 1813P

4. 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. September 14, 2020. Accessed November 1, 2024. https://investors.essapharma.com/2020-09-14-ESSA-Pharma-Announces-Fast-Track-Designation-Granted-by-the-FDA-to-EPI-7386-for-the-Treatment-of-Metastatic-Castration-Resistant-Prostate-Cancer