ESSA Pharma Updates Phase 1/2 Masofaniten (EPI-7386) Data at 2024 ESMO Congress

ESSA Pharma Inc., a clinical-stage pharmaceutical company, has presented updated data from its Phase 1/2 study on masofaniten (formerly known as EPI-7386) combined with enzalutamide for treating metastatic castration-resistant prostate cancer (mCRPC). The data was showcased at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain.

Masofaniten is a pioneering N-terminal domain androgen receptor (AR) inhibitor designed to combat prostate cancer by hindering androgen activity. The latest findings from the Phase 1 dose escalation study indicate that the combination of masofaniten with enzalutamide continues to be well tolerated, demonstrating significant and lasting reductions in prostate-specific antigen (PSA) levels among mCRPC patients. After a follow-up period of 15.2 months, neither the median time to PSA progression nor radiographic progression-free survival has been reached, contrasting positively with historical data for enzalutamide alone in similar patient populations.

David Parkinson, MD, President and CEO of ESSA, expressed satisfaction over the maturation of the data and emphasized the ongoing enrollment in the Phase 2 dose expansion study. This study is currently active at 33 sites across the US, Canada, and Australia, with an additional 22 sites planned in Europe. Further updates are anticipated in 2025.

The Phase 1/2 trial is a multicenter, open-label study focusing on mCRPC patients who have undergone androgen deprivation therapy and are new to second-generation antiandrogens, though some may have had prior chemotherapy for metastatic hormone-sensitive prostate cancer. The presented data encompasses 18 patients across four cohorts within the Phase 1 dose escalation segment. It was found that masofaniten does not alter the exposure level of enzalutamide, allowing the full prescribed dose of 160 mg to be used in combination, while enzalutamide reduces masofaniten exposure. However, twice-daily dosing of masofaniten mitigates this reduction, maintaining clinically relevant drug levels.

Safety evaluations revealed that masofaniten combined with enzalutamide is well-tolerated at tested doses, with most adverse events being mild (Grades 1 and 2) and linked to either AR inhibition or gastrointestinal issues. One Grade 3 rash was reported in Cohort 4, leading to an increase in the cohort size. No further dose-limiting toxicities emerged, hence the maximum tolerated dose was not determined. The recommended Phase 2 combination doses were established as masofaniten 600 mg twice daily and enzalutamide 160 mg once daily.

For efficacy, the data from 16 evaluable patients showed rapid, deep, and enduring reductions in PSA levels, irrespective of previous chemotherapy. Remarkably, 88% of patients achieved a PSA reduction of 90%, 69% of them within 90 days, and 63% reached PSA levels below 0.2 ng/mL. With a median follow-up of 15.2 months, the median time to PSA progression and radiographic progression-free survival remains undetermined.

The Phase 2 portion of this study is a randomized, open-label, two-arm trial comparing the combination of masofaniten and enzalutamide against enzalutamide alone in mCRPC patients who are naïve to second-generation anti-androgens. Enrollment is ongoing in North America and Australia, with European sites to follow.

Masofaniten is a selective oral inhibitor targeting the N-terminal domain of the AR, disrupting the AR signaling pathway crucial for prostate cancer growth. This mechanism is unique as it targets a region of the AR not addressed by current therapies. Ongoing clinical trials, including a Phase 2 combination trial and a Phase 1 monotherapy study, continue to evaluate its efficacy. The U.S. FDA has granted Fast Track designation to masofaniten for treating mCRPC resistant to standard therapies. ESSA Pharma retains global rights to masofaniten, reflecting its commitment to advancing prostate cancer treatment.