Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Datroway: genotox, carcinogenicity and repro: done or skipped?
datopotamab deruxtecan · Trop-2
Genotoxicity
Not conducted with ADC; DXd Ames negative, clastogenic in vitro chromosome aberration and in vivo rat micronucleus
“In genetic toxicology studies, deruxtecan was not mutagenic in an Ames assay but demonstrated clastogenic potential in an in vitro Chinese hamster lung chromosome aberration assay and an in vivo rat bone marrow micronucleus assay.”
Carcinogenicity
Not conducted (not warranted, advanced cancer)
“Carcinogenicity studies are not warranted to support the current application.”
Reproductive & developmental
Not conducted (genotoxic payload); testis/ovary findings in rat; embryo-fetal toxicity warning
“The Applicant did not conduct fertility or embryo-fetal development toxicology studies with datopotamab deruxtecan as DXd is genotoxic and affects actively dividing cells, and therefore, these studies are not warranted to support the proposed indication.”
Safety pharmacology
Stand-alone monkey CV/respiratory/neuro study plus repeat-dose endpoints; DXd hERG negative up to 10 µM
“Datopotamab deruxtecan did not have significant effects on cardiovascular, respiratory, or neurobehavior in safety pharmacology studies in monkeys.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22Conducted: calicheamicin positive in Ames and in vitro micronucleus; ADC clastogenic in mouse micronucleus
Decnupaz
pivekimab sunirine · CD123Not conducted with ADC (ICH S9); FGN849 positive in Ames TA102, in vitro and in vivo micronucleus
Elahere
mirvetuximab soravtansine · FRαNot conducted with ADC; DM4 and S-methyl-DM4 Ames negative, rat bone marrow micronucleus positive
Emrelis
telisotuzumab vedotin · c-MetNot conducted with ADC; MMAE aneugenic (positive rat micronucleus), Ames and mouse lymphoma negative
Enhertu
fam-trastuzumab deruxtecan · HER2Not conducted with ADC; DXd clastogenic (rat micronucleus, CHL chromosome aberration), Ames negative
Kadcyla
ado-trastuzumab emtansine · HER2Conducted on DM1: Ames negative; rat micronucleus positive (aneugenic/clastogenic); monkey micronucleus inconclusive
Mylotarg
gemtuzumab ozogamicin · CD33Conducted: ADC clastogenic in mouse micronucleus; free calicheamicin DMH mutagenic and clastogenic in vitro
Padcev
enfortumab vedotin · Nectin-4Not conducted with ADC; MMAE Ames and mouse lymphoma negative, rat micronucleus positive (aneugenic)
Polivy
polatuzumab vedotin · CD79bNot conducted with ADC; MMAE Ames and mouse lymphoma negative, rat micronucleus positive (aneugenic)
Tivdak
tisotumab vedotin · Tissue factorNot conducted with ADC; MMAE: Ames and mouse lymphoma negative, rat micronucleus positive (aneugenic)
Trodelvy
sacituzumab govitecan · Trop-2Not conducted with ADC; SN-38 Ames negative, in vitro micronucleus positive (clastogenic)
Zynlonta
loncastuximab tesirine · CD19Not conducted with ADC; SG3199 clastogenic in vitro (micronucleus, chromosome aberration); Ames not assessable (cytotoxicity)