Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Elahere: which tox species, and why?
mirvetuximab soravtansine · FRα
Species
Cynomolgus monkey (general tox); rabbit for ocular tox; DM4 payload in monkey and mouse
“The monkey was demonstrated to be the most appropriate animal species for toxicological evaluation of MIRV based on FOLR1 gene sequence homology assessments, in vitro binding assays, and IHC analysis of FRα protein expression on fresh frozen tissue sections using MIRV.”
Why that species
Binds human and monkey FRα with similar affinity (98% homology); no binding to mouse or rat FRα; similar TCR staining
“MIRV (and M9346A) cross-reacts only with rhesus and cynomolgus monkey FRα, out of toxicological species.”
Surrogate molecule
No surrogate; clinical ADC in monkey and rabbit (ocular); free DM4 in non-GLP single-dose studies
“A 10-week GLP compliant repeat-dose toxicity study with mirvetuximab soravtansine was conducted in cynomolgus monkey using the clinical IV route of administration, and the payload DM4 was assessed in cynomolgus monkey in a non-GLP single IV dose toxicity study.”
Species: general tox
Cynomolgus monkey (10-week GLP study); DM4 payload single-dose in monkey
“A 10-week GLP compliant repeat-dose toxicity study with mirvetuximab soravtansine was conducted in cynomolgus monkey using the clinical IV route of administration, and the payload DM4 was assessed in cynomolgus monkey in a non-GLP single IV dose toxicity study.”
Species: DART
Not conducted
“No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine.”
Species: carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not needed to support the advanced cancer indication, consistent with ICH S9 guidance.”
Surrogate used in
No surrogate used; clinical ADC cross-reacts with rhesus and cynomolgus monkey FRα only
“MIRV (and M9346A) cross-reacts only with rhesus and cynomolgus monkey FRα, out of toxicological species.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22Rat and cynomolgus monkey (neither cross-reactive; target-independent toxicity only)
Datroway
datopotamab deruxtecan · Trop-2Rat (non-binding) and cynomolgus monkey (relevant); DXd payload in rat and monkey
Decnupaz
pivekimab sunirine · CD123Cynomolgus monkey (no CD123 cross-reactivity; off-target/payload toxicity) plus rat for FGN849 payload
Emrelis
telisotuzumab vedotin · c-MetCynomolgus monkey (relevant); rat non-binding (exploratory, MMAE-related effects)
Enhertu
fam-trastuzumab deruxtecan · HER2Cynomolgus monkey (relevant) plus rat (non-binding species)
Kadcyla
ado-trastuzumab emtansine · HER2Rat and cynomolgus monkey (monkey pharmacologically relevant; long-term studies in monkey)
Mylotarg
gemtuzumab ozogamicin · CD33Rat and cynomolgus monkey (neither pharmacologically relevant; no CD33 cross-reactivity)
Padcev
enfortumab vedotin · Nectin-4Rat and cynomolgus monkey
Polivy
polatuzumab vedotin · CD79bRat and cynomolgus monkey (monkey with clinical ADC plus monkey-CD79b surrogate ADC)
Tivdak
tisotumab vedotin · Tissue factorCynomolgus monkey only for ADC; rat and monkey for MMAE payload
Trodelvy
sacituzumab govitecan · Trop-2Cynomolgus monkey only (mouse for target-independent toxicity only)
Zynlonta
loncastuximab tesirine · CD19No pharmacologically relevant species; cynomolgus monkey (non-binding) for ADC; rat and dog for payload SG3199