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

Imlunestrant (LY3484356) is a next‐generation orally bioavailable selective estrogen receptor degrader being investigated for the treatment of estrogen receptor–positive advanced breast and endometrial cancers. This Phase 1, open‐label, 2‐part study evaluated the disposition and absolute bioavailability of [ 14 C]‐imlunestrant in 16 US‐based healthy women (aged 36‐65 years) of non–childbearing potential. Part 1 participants (N = 8) received an oral dose of 400‐mg [ 14 C]‐imlunestrant solution (100 µCi). Part 2 participants (N = 8) received an oral dose of 2 × 200‐mg imlunestrant tablets followed by approximately 45 µg [ 14 C]‐imlunestrant (approximately 1 µCi) given as a 15‐minutes infusion 4 hour later. Blood, fecal, and urine samples were collected. Total radioactivity was primarily eliminated in feces (97.3%) with trace amounts recovered in urine (0.278%), suggesting minimal renal clearance. Imlunestrant accounted for most of the radioactive dose in feces (61.8%), followed by metabolite M2 (20.9%), metabolites M5 + M10 (coeluted), M7, M8, M9, and M11 (5.1% or less for each). Absolute bioavailability of imlunestrant after oral administration relative to intravenous administration was 10.9% based on dose‐normalized area under the concentration–time curve from time zero to infinite time. Imlunestrant was well tolerated as an oral solution or as a tablet/intravenous dose. Eight participants reported mild/moderate treatment‐related adverse events that resolved by the end of the study.