Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Elahere: genotox, carcinogenicity and repro: done or skipped?
mirvetuximab soravtansine · FRα
Genotoxicity
Not conducted with ADC; DM4 and S-methyl-DM4 Ames negative, rat bone marrow micronucleus positive
“DM4 and S-methyl-DM4 were negative in the vitro bacterial reverse mutation assay but positive in the in vivo rat bone marrow micronucleus assay.”
Carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not needed to support the advanced cancer indication, consistent with ICH S9 guidance.”
Reproductive & developmental
Not conducted (ICH S9); DM4 genotoxic, embryotoxicity expected; FRα mutations linked to birth defects
“No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine.”
Safety pharmacology
Incorporated into repeat-dose monkey study (ECG, clinical observation); DM4/S-methyl-DM4 hERG IC50 >60 µM
“Additionally, mirvetuximab soravtansine did not have effects on the nervous, cardiovascular, or respiratory systems in monkeys after repeated IV dosing up to 8 mg/kg (4-fold the exposures at the recommended dose based on AUC) based on ECG analysis and clinical observation.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22Conducted: calicheamicin positive in Ames and in vitro micronucleus; ADC clastogenic in mouse micronucleus
Datroway
datopotamab deruxtecan · Trop-2Not conducted with ADC; DXd Ames negative, clastogenic in vitro chromosome aberration and in vivo rat micronucleus
Decnupaz
pivekimab sunirine · CD123Not conducted with ADC (ICH S9); FGN849 positive in Ames TA102, in vitro and in vivo micronucleus
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)