Imdelltra: which tox species, and why?

“The cynomolgus monkey was selected for toxicology testing given that tarlatamab similarly bound human and monkey CD3 and DLL3 but did not bind CD3 from other species.”

“However, the monkey may not be pharmacologically relevant considering DLL3 is expressed intracellularly in normal cells and tissues.”

“Following the proposal of the FDA, a murine surrogate molecule of tarlatamab, designated muS757, was developed to evaluate potential effects of a DLL3-targeting BiTE molecule on embryofetal development in mice.”

“The nonclinical safety assessment of tarlatamab was based on a 10-day exploratory as well as 28-day GLP and 3-month GLP repeat-dose IV toxicology studies with once weekly doses of up to 4500 µg/kg.”

“Following the proposal of the FDA, a murine surrogate molecule of tarlatamab, designated muS757, was developed to evaluate potential effects of a DLL3-targeting BiTE molecule on embryofetal development in mice.”

“No carcinogenicity studies have been conducted nor are any planned in accordance with ICH S9 (ICH, 2010).”

“Two administrations of a tarlatamab surrogate, mus757, that binds mouse CD3 and DLL3, to pregnant mice on gestational days (GD) 6 and GD 13 did not result in maternal toxicity or embryo-fetal development toxicity at doses ≤4500 µg/kg.”