Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Datroway: which tox species, and why?
datopotamab deruxtecan · Trop-2
Species
Rat (non-binding) and cynomolgus monkey (relevant); DXd payload in rat and monkey
“Though datopotamab deruxtecan did not bind rat Trop2 in an in vitro assay, the monkey is a pharmacologically relevant species considering datopotamab deruxtecan demonstrated similar binding to human and monkey Trop2.”
Why that species
Similar binding to human and monkey Trop2; weak to no binding to mouse and rat Trop2
“Datopotamab deruxtecan bound to human and monkey Trop2 similarly in an ELISA-based assay but demonstrated weak to no binding to mouse and rat Trop2.”
Surrogate molecule
No surrogate; clinical ADC in rat and monkey; DXd payload in GLP 1-month rat and monkey studies
“The toxicity of DXd was also evaluated in GLP-compliant 1-month repeat-dose toxicology studies in rats and monkeys.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22Rat and cynomolgus monkey (neither cross-reactive; target-independent toxicity only)
Decnupaz
pivekimab sunirine · CD123Cynomolgus monkey (no CD123 cross-reactivity; off-target/payload toxicity) plus rat for FGN849 payload
Elahere
mirvetuximab soravtansine · FRαCynomolgus monkey (general tox); rabbit for ocular tox; DM4 payload in monkey and mouse
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