ESMO 2024: phase 1/2 trial of oral masofaniten (EPI-7386) plus Enzalutamide compared to Enzalutamide alone in men with mCRPC

[Maxone73]

This looks promising.

The trial enrolled 18 patients who were on androgen deprivation therapy but had not received prior AR pathway inhibitors; some had received chemotherapy in the hormone-sensitive setting. Patients were treated with escalating doses of Masofaniten (EPI-7386), up to 600 mg twice daily, alongside enzalutamide (160 mg once daily). The combination was well-tolerated, exhibiting a safety profile consistent with enzalutamide alone. The most common treatment-related adverse events were mild to moderate fatigue, hypertriglyceridemia, hypercholesterolemia, and diarrhea, with only one Grade 3 rash reported.

Efficacy outcomes were promising: 88% of evaluable patients achieved a PSA decline of over 90%, and 63% reached PSA levels below 0.2 ng/mL. Among those with measurable disease, 60% experienced a partial response, while the remaining had stable disease. These deep and durable responses were observed regardless of dosing regimen or prior chemotherapy status. Pharmacokinetic analyses indicated that enzalutamide did not affect Masofaniten exposure, allowing for full dosing of enzalutamide.

With a median follow-up of 15.2 months, over 60% of patients remained on treatment, and time-to-event parameters compared favorably with historical data from trials like AFFIRM and PREVAIL, which assessed enzalutamide monotherapy.

urotoday.com/conference-hig...

[God_Loves_Me]

Important Note :

Of note, 78% of mCRPC patients enrolled in the Phase 1 part presented 2 or more risks of early failure to enzalutamide single agent treatment.