Treatment
toxicity, overdose
Patients received oral M8891 in 21-day cycles at doses of 7–80 mg once daily. The starting dose of 7 mg once daily was based on the dog highest non-severely toxic dose of 0.75 mg/kg/day divided by a safety factor of 6, which equated to a human dose of 7.5 mg (rounded to 7 mg) for a participant of 60 kg bodyweight. Safety Monitoring Committee (SMC) decisions on subsequent dose levels were supported by a BLRM with overdose control. In addition, the SMC could decide to switch from a once daily to twice daily dosing schedule if data suggested insufficient exposure (pharmacokinetics) and target engagement (pharmacodynamics) after completion of the dose-limiting toxicity (DLT) period of the third once daily dosing cohort (or at a later time) or if evidence suggested that 