Dr Kyriakopoulos on the Initial Activity and Safety of Masofaniten Plus Enzalutamide in mCRPC

Christos Kyriakopoulos, MD, medical oncologist, associate professor, Department of Medicine, Division of Hematology, Medical Oncology and Palliative Care, the University of Wisconsin School of Medicine and Public Health, discusses initial safety, pharmacokinetic, and efficacy findings with the addition of masofaniten (EPI-7386) to enzalutamide (Xtandi) in metastatic castration-resistant prostate cancer (mCRPC).

A multicenter phase 1/2 trial (NCT05075577) evaluated patients with mCRPC who had not been previously exposed to second-generation anti-androgen therapy. In the phase 1 dose equilibrium portion, patients were randomly assigned to received either 1 of 4 escalating doses of enzalutamide at 120 mg or 160 mg and masofaniten at 600 mg every day or twice a day. Primary end points included safety and pharmacokinetics.

Results presented at the 2024 Genitourinary Cancers Symposium showed that the combination therapy was safe and tolerable, with primarily low-grade AEs and a safety profile consistent with that of enzalutamide monotherapy, Kyriakopoulos reports. The most frequently observed AEs attributed to masofaniten were related to androgen receptor inhibition and gastrointestinal tract irritation. One grade 3 dose-limiting toxicity of maculopapular rash was observed at dose level 4, and the patient discontinued study treatment. However, no serious AEs were observed, Kyriakopoulos adds. The recommended phase 2 dose of enzalutamide was established as the full approved dose of enzalutamide at 160 mg per day and 600 mg of masofaniten twice a day to compensate for the reduction in exposure caused by enzalutamide, he states.

Notably, a high percentage of patients treated with masofaniten plus enzalutamide achieved significant declines in PSA levels regardless of the starting PSA levels, Kyriakopoulos continues. At a median follow-up of 11.1 months, 81% of patients experienced a decline greater than 90% and 60% achieved PSA90 within 90 days, Kyriakopoulos details. Additionally, 88% of patients achieved a 50% reduction of PSA from baseline (PSA50), and 56% achieved a PSA level less than 0.2 ng/ml, he says. Data on disease progression and other efficacy findings were still immature at the time of analysis, Kyriakopoulos notes.

A total of 13 patients are still on treatment, Kyriakopoulos continues. Reasons for treatment discontinuation included disease progression (n = 3), development of a non-cancer related brain abscesses (n = 1) , and non-cancer related death (n = 1), Kyriakopoulos says. Notably, the latter 2 patients had reached PSA50, Kyriakopoulos states.

The phase 2 portion of the study is actively enrolling patients from this population at multiple sites across the United States, Canada, and Australia.