Imfinzi: which tox species, and why?

“The cynomolgus monkey was found to be the only pharmacological relevant nonclinical species for evaluation of local and systemic toxicities of durvalumab.”

“Durvalumab was found to only bind to human and cynomolgus monkey PD-L1, and the cynomolgus monkey was found to be the only relevant nonclinical species for the safety and toxicity studies.”

“For the PD studies, either a model of immunodeficient mice inoculated with a mixture of human tumour cell lines expressing B7- H1 (PD-L1) and human T-cells alloreactive to the human tumour cell lines or in a syngeneic mouse model using a mouse surrogate monoclonal antibody against mouse PD-L1.”

“General toxicology studies included evaluation of durvalumab in Cynomolgus monkeys for up to 13 weeks.”

“The potential effects of durvalumab on pregnancy outcome, embryo-fetal development, survival, and postnatal development of the offspring were evaluated in an enhanced pre-and postnatal development study in cynomolgus monkeys (ePPND study design).”

“The carcinogenic and genotoxic potential of durvalumab have not been evaluated.”

“in a syngeneic mouse model using a mouse surrogate monoclonal antibody against mouse PD-L1.”