Pharmacokinetic Assessments
In the single-agent dose-escalation stage, pharmacokinetic samples were collected at cycle 1 day −7 predose and then at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 28, 72, 96, and 168 hours after dosing to characterize the single-dose pharmacokinetic profile and estimate the terminal half-life. Samples to determine the steady-state pharmacokinetic profile were collected at cycle 2 day 1 (after 28 days of daily giredestrant) predose and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after dosing. Metabolite identification was conducted following the first dose (cycle 1 day −7) and at steady state (cycle 2 day 1) in 6 patients (3 patients at 90 mg and 3 at 250 mg). Plasma samples were pooled across patients and timepoints.The cytochrome P450 (CYP) 3A induction potential of giredestrant was evaluated Giredestrant concentrations in urine samples were measured at cycle 1 day 1 predose and cycle 2 day 1 at 0–8 hours postdose. Urine samples were collected from 13 patients (7 patients at 30 mg, 5 at 100 mg, 1 at 250 mg).