Lumakras: how was the first human dose set?

“The mean observed sotorasib clinical exposures from 180, 360, 720, and 960 mg once daily (QD) dosing in subjects (Study 20170543) were lower than the exposures observed at the STD10 of 180 mg/kg in rats in the 3-month GLP repeat-dose toxicology study (Study 150432), but higher than the exposures observed at the HNSTD of 1000 mg/kg/day in dogs”

“In rats, renal toxicity including minimal to marked histologic tubular degeneration/necrosis and increased kidney weight, urea nitrogen, creatinine, and urinary biomarkers of renal tubular injury were present at doses resulting in exposures approximately ≥ 0.5 times the human AUC at the clinical dose of 960 mg.”