Masofaniten plus enzalutamide shows promise in mCRPC

The combination of oral masofaniten (formerly EPI-7386) and enzalutamide (Xtandi) was well tolerated and elicited durable reductions in PSA levels in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from a phase 1/2 trial (NCT05075577) recently presented at both the 2023 European Society for Medical Oncology Annual Congress¹ and the 30th Annual Prostate Cancer Foundation Scientific Retreat.²

Among the first 3 cohorts of the dose escalation phase of the trial, 90% (9 of 10 patients) of patients achieved PSA50 (decrease of 50% or greater from baseline) and PSA90 (decrease of 90% or greater from baseline), 80% of patients achieved PSA90 in less than 90 days, and 70% of patients achieved a PSA of less than 0.2 mg/mL.

The presentations included updated data from the dose escalation portion of the trial, in which patients received either 600 mg of once daily masofaniten and 120 mg of enzalutamide, 800 mg of once daily masofaniten and 120 mg of enzalutamide, 600 mg of twice daily masofaniten and 120 mg of enzalutamide, or 600 mg twice daily of masofaniten and 160 mg of enzalutamide.

Overall, the combination demonstrated safety and tolerability among all 4 dose levels assessed through 21 cycles of dosing in some patients. The most common adverse events (AEs) were grade 1 and 2 and were most frequently related to AR inhibition or gastrointestinal tract irritation. In cohort 4, the investigators observed one grade 3 rash that was deemed as probably related to treatment.

Regarding efficacy, the combination demonstrated rapid, durable, and deep reductions in PSA. Among the first 3 cohorts of the dose escalation phase of the trial, 90% (9 of 10 patients) of patients achieved PSA50 (decrease of 50% or greater from baseline) and PSA90 (decrease of 90% or greater from baseline), 80% of patients achieved PSA90 in less than 90 days, and 70% of patients achieved a PSA of less than 0.2 mg/mL.

Among patients across all 4 cohorts of the study, 88% (14/16 patients) achieved PSA50, 81% (13/16 patients) achieved PSA90, 69% (11/16 patients) achieved PSA90 in less than 90 days, and 56% (9/16 patients) achieved a PSA of less than 0.2 mg/mL.

"This poster, presented today at the Prostate Cancer Foundation Scientific Retreat, contains updated cohort 4 data from the dose escalation portion of our phase 1/2 study evaluating the combination of masofaniten and enzalutamide in patients with metastatic castration-resistant prostate cancer," David Parkinson, MD, president and CEO of ESSA, the developer of masofaniten, stated in a news release."²

"[Although] the data for patients in cohort 4 are still maturing, these updated data continue to demonstrate that the combination is well tolerated and leads to deep and durable reductions in prostate-specific antigen, including in cohort 4, which reflects the dosing regimen that is being evaluated in the phase 2 dose expansion. We look forward to providing future updates," added Parkinson.

The study enrolled patients with mCRPC who had received prior androgen deprivation therapy and who were naïve to second-generation antiandrogens. Patients with prior docetaxel in the metastatic hormone-sensitive setting were also eligible for inclusion.

At the time of data cutoff, 18 patients were evaluable for safety and 16 patients were evaluable for efficacy. Of the 18 patients enrolled, 5 discontinued treatment due to disease progression (n = 3), brain abscess not related to treatment (n = 1), and non-cancer related death (n = 1).

Based on data from phase 1 of the study, the investigators recommended a phase 2 dose level of 600 mg twice daily of masofaniten and 160 mg once daily of enzalutamide.

The randomized phase 2 expansion portion of the study is currently enrolling participants.

References

1. 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

2. ESSA Pharma presents updated phase 1 masofaniten (EPI-7386) clinical data at the 30th Annual Prostate Cancer Foundation Scientific Retreat. News release. ESSA Pharma Inc. October 26, 2023. Accessed October 27, 2023. https://www.prnewswire.com/news-releases/essa-pharma-presents-updated-phase-1-masofaniten-epi-7386-clinical-data-at-the-30th-annual-prostate-cancer-foundation-scientific-retreat-301969481.html