Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Tivdak: which tox species, and why?
tisotumab vedotin · Tissue factor
Species
Cynomolgus monkey only for ADC; rat and monkey for MMAE payload
“The data suggests that the cynomolgus monkey was the only relevant toxicological species.”
Why that species
Tisotumab binds human and cynomolgus TF similarly; no binding to mouse, rat, rabbit, pig or dog TF
“Tisotumab did not bind to mouse, rat, rabbit, pig, or dog TF.”
Surrogate molecule
No surrogate; clinical ADC tested in monkey, payload (MMAE) separately in rat and monkey
“A GLP compliant repeat-dose toxicology study with tisotumab vedotin was conducted in monkeys (13-week), and the payload was assessed in rats (4-week) and monkeys (11-week) using the clinical intravenous route of administration.”
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
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)
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