Adcetris
brentuximab vedotin · CD30Rat and cynomolgus monkey (monkey the antigen-binding species)
Zynlonta: which tox species, and why?
loncastuximab tesirine · CD19
Species
No pharmacologically relevant species; cynomolgus monkey (non-binding) for ADC; rat and dog for payload SG3199
“No pharmacologically relevant nonclinical species for safety evaluation—as defined in ICH S6(R1)—exists for loncastuximab tesirine, due its antibody component being selective for human CD19.”
Why that species
Antibody not cross-reactive with any nonclinical CD19; monkey chosen for PK predictivity, lower ADA impact, and PBD class-toxicity translation
“The monoclonal antibody (mAb) component of loncastuximab tesirine, RB4v1.2, is selective for human CD19 and not cross‐reactive with CD19 from any nonclinical species.”
Surrogate molecule
No surrogate; clinical ADC in non-binding monkey (off-target only), free payload SG3199 in rat and dog
“Importantly, on‐target (ie, CD19‐mediated) toxicity cannot be evaluated in this or any other nonclinical species; however, a considerable body of data on the nonclinical and clinical safety of CD19‐ and CD20‐specific B‐cell‐depleting agents exists.”
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)
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)