Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Decnupaz: which tox species, and why?
pivekimab sunirine · CD123
Species
Cynomolgus monkey (no CD123 cross-reactivity; off-target/payload toxicity) plus rat for FGN849 payload
“pivekimab sunirine does not cross-react with CD123 in standard animal species used for toxicology studies (mouse, rat, or cynomolgus monkey).”
Why that species
No CD123 cross-reactivity in standard species; monkey used for off-target/payload effects; weaker monkey TCR staining
“PVEK produced less intense and less frequently observed staining in monkey mononuclear cells.”
Surrogate molecule
No surrogate; clinical ADC tested in monkey; FGN849 payload tested alone in rats
“Additional studies were conducted with the FGN849 payload alone in rats, including single-dose studies (doses of 0, 15, or 25 μg/kg) and 5-day repeat-dose studies (doses of 0, 1, or 3 μg/kg daily for five days).”
Species: general tox
Cynomolgus monkey only (single-dose and 13-week GLP studies)
“Studies included single-dose GLP toxicology studies with pivekimab sunirine in cynomolgus monkeys (doses of 0, 0.1, 0.3, or 0.6 mg/kg) with a 28-day recovery period and a 13-week repeat-dose GLP study with pivekimab sunirine in cynomolgus monkeys (0, 0.01, 0.03, or 0.1 mg/kg administered once every three weeks for five doses) with an 8-week recovery period.”
Species: DART
Not conducted (ICH S9 and FDA feedback)
“No reproductive and developmental studies have been conducted with PVEK, in accordance with ICH S9 and FDA feedback (Reference ID: 4704103).”
Species: carcinogenicity
Not conducted (ICH S9)
“In accordance with ICH S9, carcinogenicity studies have not been conducted with PVEK.”
Surrogate used in
No surrogate used; clinical ADC does not cross-react with CD123 in mouse, rat or cynomolgus monkey
“pivekimab sunirine does not cross-react with CD123 in standard animal species used for toxicology studies (mouse, rat, or cynomolgus monkey).”
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
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