Imjudo: genotox, carcinogenicity and repro: done or skipped?

“No studies were conducted in accordance with ICH S6(R1).”

“The Applicant did not conduct carcinogenicity or genetic toxicology studies as they are generally not appropriate for antibody therapies.”

“Under the conditions tested, there were no effects on maternal toxicity or embryo‐fetal mortality or malformations at doses up to 30 mg/kg administered once weekly during the period of organogenesis from GD20 to GD48 in an embryo‐fetal toxicity study in cynomolgus monkeys.”

“The FDA agrees that there were no tremelimumab‐related effects on cardiovascular, respiration, or central nervous system parameters in male and female cynomolgus monkeys at doses up to 50 mg/kg administered once weekly for up to 6 months.”

“The Applicant did not conduct carcinogenicity or genetic toxicology studies as they are generally not appropriate for antibody therapies.”

“The Applicant did not conduct carcinogenicity or genetic toxicology studies as they are generally not appropriate for antibody therapies.”

“The Applicant did not conduct carcinogenicity or genetic toxicology studies as they are generally not appropriate for antibody therapies.”

“The carcinogenic and genotoxic potential of tremelimumab-actl have not been evaluated.”

“Carcinogenic potential of tremelimumab was not evaluated, and this is acceptable given the indication sought in the treatment of unresectable hepatocellular carcinoma (uHCC).”

“ECG, heart rate, blood pressure and vital signs (respiration rate and body temperature) was evaluated twice pre-dose and 5 min post dose in the GLP single dose study (tmax) and on several occasions during the dosing and recovery phase in the two repeat-dose studies. No dose-related changes from normal were observed in any study or on any occasion.”