Methods
SOLID TUMORS
Period 1: patients with locally advanced or metastatic solid tumors received ‘cocktail’: caffeine 200 mg, omeprazole 20 mg, and midazolam 2 mg (single dose); period 2: after 7- to 14-day washout, patients received adavosertib 225 mg twice daily on days 1–3 (five doses), with cocktail on day 3. After cocktail alone or in combination with adavosertib administration, 24-h pharmacokinetic sampling occurred for probe substrates and their respective metabolites paraxanthine, 5-hydroxyomeprazole (5-HO), and 1′-hydroxymidazolam (1′-HM). Safety was assessed throughout.