Kadcyla: what was done before first-in-human, and what came after?

“In view of these results, the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys was 10 mg/kg for four injections every 3 weeks which was below the no observable adverse effect level in that species and below one-tenth of the severely toxic dose in rats, this information was used to determine a Phase I starting dose in humans.”

“the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys was 10 mg/kg for four injections every 3 weeks which was below the no observable adverse effect level in that species and below one-tenth of the severely toxic dose in rats, this information was used to determine a Phase I starting dose in humans.”

“The animals received doses of TDM1 of 0 1, 3, or 10 mg/kg once every three weeks for 8 doses. Half the monkeys were allowed to recover for six weeks after the last dose.”

“The Applicant did a second multidose toxicology study in Cynomolgus monkeys (study 07-0653). The animals received doses of TDM1 of 0 1, 3, or 10 mg/kg once every three weeks for 8 doses.”

“Based on these findings and consistent with ICH S9, embryo-fetal developmental toxicity studies were not required for the indicated patient population.”

“Based on these findings and consistent with ICH S9, embryo-fetal developmental toxicity studies were not required for the indicated patient population.”

“After consultation with the FDA, the Applicant did not conduct new reproductive toxicity studies with trastuzumab emtansine. The small molecule component, DM1, is a microtubule inhibitor which is genotoxic.”

“Carcinogenicity studies have not been conducted with ado-trastuzumab emtansine.”

“Not required and not submitted.”

“Not required and not submitted.”