Rybrevant: which tox species, and why?

“The cynomolgus monkey was selected as the only pharmacologically relevant species for the nonclinical pharmacokinetic (PK) and toxicology assessments of amivantamab based on a comparison of sequence homology, cross-species comparisons of relative target-binding affinities, and functional activity in cell-based assays.”

“Amivantamab bound to the ECD of human and cynomolgus monkey EGFR and MET with similar EC50 values (Table 3), but not to the ECD of rat EGFR or MET (data not included in review).”

“The cynomolgus monkey is considered the pharmacologically relevant species for the toxicology program of amivantamab (see Section 0, Safety Pharmacology).”

“Janssen conducted a GLP-compliant 13-week toxicology study in cynomolgus monkeys.”

“Rather than conducting a dedicated embryofetal development study, Janssen provided a weight-of-evidence-based assessment of the potential for amivantamab to cause reproductive and embryofetal toxicity.”

“In addition, Janssen did not conduct dedicated studies to assess fertility or carcinogenicity as these studies are not necessary to support the development of a drug intended to treat patients with advanced cancer.”

“GLP-compliant study reports for both rat embryofetal development and fertility and early embryonic studies of lazertinib, a small molecule EGFR inhibitor; and an embryofetal development study in cynomolgus monkeys using zalutumumab, an anti-EGFR monoclonal antibody.”