ESSA Discontinues Phase 2 Study of Masofaniten Plus Enzalutamide in mCRPC

The phase 2 study (NCT05075577) that was examining the novel androgen receptor inhibitor masofaniten (EPI-7386) in combination with enzalutamide (Xtandi) vs enzalutamide monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) who had not received second-generation antiandrogens has been discontinued. Findings from a futility analysis showed that there was a low likelihood of the study meeting its prespecified primary end point of a prostate-specific antigen (PSA) response of at least 90% (PSA90).¹

The decision, which was mutually agreed upon by senior management and the board of directors of ESSA Pharma, was based on findings from an interim review of the safety, efficacy, and pharmacokinetic data from the trial. Results from the study showed that patients who received the combination experienced a PSA90 at a rate of 64% compared with 73% in the monotherapy arm. The proportions of patients who achieved a PSA response of at least 50% (PSA50) were 88% and 87%, respectively.

At 90 days, the PSA50 response rates in the masofaniten plus enzalutamide and enzalutamide monotherapy arms were 93% and 86%, respectively. The 90-day PSA90 response rates were 67% and 71%, respectively.

The interim efficacy analysis included 52 patients who had at least 1 PSA measurement after baseline and 41 patients who completed a minimum of 3 months of follow-up. The study was planned to enroll approximately 120 patients: 80 in the combination arm and 40 in the monotherapy arm.

“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,” David Parkinson, MD, president and chief executive officer of ESSA, stated in a news release. “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.”

The open-label phase 2 study enrolled adult patients with metastatic mCRPC who were naive to second-generation antiandrogens in the United States, Canada, Australia, and France. Other key eligibility criteria 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 with luteinizing hormone-releasing hormone agonist/antagonist therapy or a history of bilateral orchiectomy, with castrate level testosterone, serum testosterone levels of 1.73 nmol/L (50 ng/dL) or less; and adequate organ function.²

During the phase 2 dose-expansion portion of the study, patients were randomly assigned 2:1 to receive oral masofaniten at a dose of 600 mg twice daily plus enzalutamide at a dose of 160 mg 4 times per day or enzalutamide monotherapy at the same dosing schedule. Patients remained on the study as long as the treatment was tolerable with no disease progression per RECIST 1.1 and/or PCWG3 criteria.¹

The primary end point in phase 2 was PSA90 response rate. Secondary end points included PSA50 response rate, 12-week PSA50 and PSA90 response rates, and time to event outcomes, which were not mature at the time of the interim analysis.^1,2

In terms of safety, masofaniten plus enzalutamide was well tolerated, and no new safety signals were observed. Masofaniten had previously received fast track designation from the FDA in September 2020 for the treatment of adult patients with mCRPC who are resistant to standard-of-care therapies. In the news release, ESSA noted that they retained all the rights to the agent globally.^1,3

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. Updated August 28, 2024. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT05075577
3. 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 November 1, 2024. https://www.essapharma.com/wp-content/uploads/2020/09/Branded_ESSInc_News-Release_Frast-Track_14SEP2020_Fnl.pdf