Disposition and Absolute Bioavailability of Oral Imlunestrant in Healthy Women: A Phase 1, Open-Label Study

Area of Science:

• Pharmacology
• Oncology
• Drug Metabolism and Pharmacokinetics

Background:

• Imlunestrant (LY3484356) is an investigational, orally bioavailable selective estrogen receptor degrader.
• It is being studied for estrogen receptor-positive advanced breast and endometrial cancers.

Purpose of the Study:

• To evaluate the disposition and absolute bioavailability of [14C]-imlunestrant in healthy women.
• To assess the safety and tolerability of imlunestrant administration via oral solution and tablet/intravenous routes.

Main Methods:

• Phase 1, open-label, 2-part study in 16 healthy women.
• Administration of an oral dose of [14C]-imlunestrant solution (Part 1) or imlunestrant tablets followed by intravenous [14C]-imlunestrant (Part 2).
• Collection and analysis of blood, fecal, and urine samples to determine drug and metabolite levels and radioactivity excretion.

Main Results:

• Total radioactivity was predominantly excreted in feces (97.3%), with minimal amounts in urine (0.278%).
• Imlunestrant was the major radioactive component in feces (61.8%), followed by metabolites M2, M5+M10, M7, M8, M9, and M11.
• Absolute bioavailability of oral imlunestrant relative to intravenous administration was 10.9%.

Conclusions:

• Imlunestrant exhibits limited renal clearance and is primarily eliminated via the fecal route.
• The absolute oral bioavailability of imlunestrant is approximately 10.9%.
• Imlunestrant was well-tolerated in healthy women, with mild to moderate treatment-related adverse events reported.