Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Besponsa: which tox species, and why?
inotuzumab ozogamicin · CD22
Species
Rat and cynomolgus monkey (neither cross-reactive; target-independent toxicity only)
“The Applicant conducted repeat-dose toxicity studies of up to 6 months duration in rats and cynomolgus monkeys to investigate the chronic toxicity of inotuzumab ozogamicin;”
Why that species
No relevant species: G544 does not bind mouse, rat, rabbit or monkey B cells; tox limited to payload-driven, target-independent effects
“G544 did not bind B cells from mouse, rat, rabbit, or cynomolgus monkey whole blood, or granulocytes, MONO, or T cells from any species evaluated, including humans.”
Surrogate molecule
No surrogate; clinical ADC in non-binding species, plus non-binding calicheamicin ADC (PF-06647259) investigative monkey study
“This study evaluated the target-independent toxicities of antibody-calicheamicin conjugates using a humanized nonbinding IgG1 monoclonal antibody conjugated to calicheamicin via the acid-labile AcBut linker (PF-06647259).”
Species: general tox
Rat and cynomolgus monkey (up to 6 months)
“The Applicant conducted repeat-dose toxicity studies of up to 6 months duration in rats and cynomolgus monkeys to investigate the chronic toxicity of inotuzumab ozogamicin;”
Species: DART
Rat and rabbit (embryo-fetal development)
“Embryo-fetal development studies were conducted in rabbits and rats.”
Species: carcinogenicity
Not conducted
“No carcinogenicity studies were conducted or required to support a marketing application for the current indication.”
Surrogate used in
No surrogate; species lack CD22 cross-reactivity, so toxicology limited to target-independent calicheamicin effects
“The lack of G544 cross-species reactivity indicates the utility of the nonclinical toxicology studies will be limited to the assessment of target-independent toxicities associated with conjugated and unconjugated calicheamicin.”
Same question, other ADCs
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)
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