ESSA Pharma Inc. presented updated clinical data from its Phase 1/2 study of masofaniten (EPI-7386) in combination with enzalutamide at the 2024 European Society for Medical Oncology (ESMO) Congress. The data highlight the potential of this novel therapeutic approach for patients with metastatic castration-resistant prostate cancer (mCRPC).
The Phase 1/2 trial is a multicenter, open-label study evaluating masofaniten plus enzalutamide in mCRPC patients who have received androgen deprivation therapy and are naïve to second-generation antiandrogens. The presented data included 18 patients in the Phase 1 dose-escalation portion. The recommended Phase 2 combination doses (RP2CDs) were identified as masofaniten 600 mg twice daily (BID) in combination with enzalutamide 160 mg once daily (QD).
Tolerability and Safety
The combination of masofaniten and enzalutamide was well-tolerated, with most adverse events being Grades 1 and 2. These were primarily related to androgen receptor (AR) inhibition or gastrointestinal tract irritation. One patient in Cohort 4 experienced a Grade 3 rash, deemed probably related to the treatment, leading to cohort expansion. The maximum tolerated dose (MTD) was not reached.
Efficacy Results
Efficacy data from 16 evaluable patients showed rapid, deep, and durable reductions in prostate-specific antigen (PSA) levels, regardless of prior chemotherapy status. Notably, 88% of patients achieved PSA50, 88% achieved PSA90, 69% achieved PSA90 in less than 90 days, and 63% achieved PSA <0.2 ng/mL. After a median follow-up of 15.2 months, the median time to PSA progression and radiographic progression-free survival have not yet been reached.
"We are pleased to be sharing more mature data from the Phase 1 dose escalation study evaluating masofaniten in combination with enzalutamide today at ESMO 2024. The combination continues to be well tolerated with prolonged reductions in circulating prostate-specific antigen ("PSA") levels in patients with metastatic castration-resistant prostate cancer ("mCRPC"). After 15.2 months of follow up, neither median time to PSA progression nor radiographic progression free survival have been reached. These data compare favorably to historical data for single agent enzalutamide treatment in the mCRPC patient population," said David Parkinson, MD, President and CEO of ESSA.
Phase 2 Dose Expansion
The randomized, open-label, two-arm Phase 2 dose expansion is currently enrolling patients. It is designed to evaluate masofaniten plus enzalutamide versus enzalutamide alone in mCRPC patients who are naïve to second-generation anti-androgens. The study is actively enrolling at approximately 33 sites in the USA, Canada, and Australia, with an additional 22 sites anticipated in Europe.
About Masofaniten
Masofaniten (formerly EPI-7386) is a first-in-class, highly selective, oral, small molecule inhibitor of the N-terminal domain (NTD) of the androgen receptor (AR). Its unique mechanism disrupts the AR signaling pathway by selectively binding to the NTD, a region not targeted by other therapies. The U.S. Food and Drug Administration has granted Fast Track designation to masofaniten for mCRPC patients resistant to standard-of-care treatment. ESSA retains all rights to masofaniten worldwide.
