Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Padcev: genotox, carcinogenicity and repro: done or skipped?
enfortumab vedotin · Nectin-4
Genotoxicity
Not conducted with ADC; MMAE Ames and mouse lymphoma negative, rat micronucleus positive (aneugenic)
“Using the standard core battery of genetic toxicology studies recommended in the ICH S2 guidance, MMAE was reported to be genotoxic in the in vivo rat bone marrow micronucleus assay through an aneugenic mechanism.”
Carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted or needed to support marketing of PADCEV in patients with advanced cancer.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
No fertility or PPND studies (ICH S9); preliminary rat EFD with ADC and MMAE EFD: embryolethal, teratogenic
“Fertility and early embryonic development studies were not conducted or needed to support marketing of PADCEV in patients with advanced cancer.”
Safety pharmacology
Incorporated into repeat-dose tox studies; MMAE hERG negative; no CV, respiratory or CNS effects
“No effect was reported on ECG, heart rate, blood pressure, respiratory or CNS endpoints.”
Genotox: Ames
MMAE payload: negative in Ames test
“MMAE was not mutagenic in the bacterial reverse mutation assay (Ames test) or the L5178Y mouse lymphoma forward mutation assay.”
Genotox: in vitro mammalian
MMAE payload: negative in L5178Y mouse lymphoma forward mutation assay
“MMAE was not mutagenic in the bacterial reverse mutation assay (Ames test) or the L5178Y mouse lymphoma forward mutation assay.”
Genotox: in vivo
MMAE payload: positive in rat bone marrow micronucleus (aneugenic)
“MMAE was genotoxic in the rat bone marrow micronucleus study through an aneugenic mechanism.”
Carcinogenicity model
Not conducted (ADC or MMAE); ICH S9, metastatic UC
“In accordance with International Council for Harmonisation (ICH) S9, carcinogenicity studies were not conducted for enfortumab vedotin as it is intended for treatment of metastatic UC.”
Carcinogenicity timing
Not required for advanced cancer; none conducted
“Carcinogenicity studies were not conducted or needed to support marketing of PADCEV in patients with advanced cancer.”
hERG / QT
MMAE: <50% hERG inhibition at >19,000-fold clinical Cmax; no significant inhibition at 10 µM
“MMAE, at concentrations greater than 19,000-fold higher than the clinically observed Cmax had limited (less than 50%) inhibition of potassium conductance via hERG channels, and at 10 µmol/L there was no significant inhibition of hERG channel activity.”
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
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
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)