Tukysa: which tox species, and why?

“Twice daily oral administration of tucatinib was assessed in repeat-dose toxicity studies for up to 3 months in rats and monkeys, consistent with the clinical route of administration and intended dosing schedule.”

“The pharmacological relevance of the toxicological species was discussed by the applicant and taking sequence homology information as well as a justification based on historical use (rat) and higher oral tolerability (monkey) into account, the chosen species were considered acceptable.”

“In a 90-day cynomolgus monkey study, males and females (6/sex/group) were administered tucatinib at 0, 2.5, 10, or 20 mg/kg/dose twice daily (5, 20, or 40 mg/kg/day) via oral gavage.”

“Twice daily oral administration of tucatinib was assessed in repeat-dose toxicity studies for up to 3 months in rats and monkeys, consistent with the clinical route of administration and intended dosing schedule.”

“The Applicant conducted pilot embryo-fetal development studies in rats and rabbits.”

“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for advanced cancer.”

“Twice daily oral administration of tucatinib was assessed in repeat-dose toxicity studies for up to 3 months in rats and monkeys, consistent with the clinical route of administration and intended dosing schedule.”