Adcetris
brentuximab vedotin · CD30Three xenograft models from human HL and ALCL cell lines
Kadcyla: animal efficacy model or human cells?
ado-trastuzumab emtansine · HER2
Efficacy evidence
HER2+ xenografts (BT-474 EI, Calu-3) and MMTV-HER2 transgenic tumor model; growth inhibition in all three at 3 to 31 mg/kg
“Trastuzumab-MCC-DM1 caused tumor growth inhibition in all three models in the dose range of 3 to 31 mg/kg, depending on the model.”
Why that model
Mouse models carrying human HER2-positive tumors (human cell-line xenografts) allowed testing of the clinical ADC
“Anti-tumor activity of trastuzumab emtansine was evaluated in three independent animal models of HER2-positive human cancers (not formally reviewed). Two of these are xenograft models using human tumor cell lines.”
Reviewer's view of the efficacy data
EMA: pharmacodynamic activity adequately characterised by the nonclinical package
“Based on the nonclinical safety data trastuzumab emtansine has been adequately characterised in terms of its pharmacodynamic activity, pharmacokinetic properties and safety profile.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22Subcutaneous xenograft and systemically disseminated ALL mouse models
Datroway
datopotamab deruxtecan · Trop-2Nude mouse xenografts of human pancreatic cancer, NSCLC and breast cancer
Decnupaz
pivekimab sunirine · CD123Two BPDCN patient-derived xenograft (PDX) models in NSG mice
Elahere
mirvetuximab soravtansine · FRαOvarian cancer xenograft mouse models (single IV dose)
Emrelis
telisotuzumab vedotin · c-Metc-Met-positive NSCLC cell line-derived and patient-derived xenograft mouse models
Enhertu
fam-trastuzumab deruxtecan · HER2HER2-positive breast cancer xenograft mouse models (e.g., KPL-4 in nude mice)
Mylotarg
gemtuzumab ozogamicin · CD33CD33+ HL-60 leukemia xenograft in mice: >80% tumor growth inhibition
Padcev
enfortumab vedotin · Nectin-4Nectin-4-expressing patient-derived bladder cancer xenografts (AG-B1, AG-B8) in mice: >75% tumor growth inhibition
Polivy
polatuzumab vedotin · CD79bHuman DLBCL and B-cell lymphoma xenografts in mice; in vitro Ramos cytotoxicity
Tivdak
tisotumab vedotin · Tissue factorCervical cancer patient-derived xenograft (PDX) models in mice
Trodelvy
sacituzumab govitecan · Trop-2Mouse xenografts bearing human Trop-2-expressing tumours
Zynlonta
loncastuximab tesirine · CD19CD19-positive human Burkitt lymphoma (Ramos, Daudi) and DLBCL (WSU-DLCL2) xenografts in immunodeficient mice