Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Polivy: genotox, carcinogenicity and repro: done or skipped?
polatuzumab vedotin · CD79b
Genotoxicity
Not conducted with ADC; MMAE Ames and mouse lymphoma negative, rat micronucleus positive (aneugenic)
“MMAE was genotoxic in the rat bone marrow micronucleus study through an aneugenic mechanism.”
Carcinogenicity
Not conducted (not warranted for indication; ICH S9)
“Carcinogenicity studies in animals have not been performed with polatuzumab vedotin or MMAE and are not warranted for the proposed indication.”
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 study (ICH S9); MMAE rat EFD embryolethal and teratogenic; testicular toxicity in rat repeat-dose
“A designated fertility study was not conducted with polatuzumab vedotin or MMAE and is not needed for the proposed indication.”
Safety pharmacology
Incorporated into rat and monkey repeat-dose studies; MMAE hERG IC50 >100 uM; no adverse effects
“Safety pharmacology assessments (neurobehavioral, cardiovascular, and respiratory) that were incorporated into the repeat-dose toxicology studies showed no polatuzumab vedotin- or surrogate ADC-induced adverse effects in monkeys.”
Genotox: Ames
MMAE: negative in Ames assay
“MMAE was not mutagenic in the bacterial reverse mutation (Ames) assay or the L5178Y mouse lymphoma forward mutation assay.”
Genotox: in vitro mammalian
MMAE: negative in L5178Y mouse lymphoma forward mutation assay
“MMAE was not mutagenic in the bacterial reverse mutation (Ames) assay or the L5178Y mouse lymphoma forward mutation assay.”
Genotox: in vivo
MMAE: positive in rat bone marrow micronucleus (aneugenic)
“MMAE was positive for genotoxicity in the in vivo rat bone marrow micronucleus study through an aneugenic mechanism.”
Carcinogenicity model
Not conducted with polatuzumab vedotin or MMAE (not warranted for the indication)
“Carcinogenicity studies in animals have not been performed with polatuzumab vedotin or MMAE and are not warranted for the proposed indication.”
Carcinogenicity timing
Not conducted with polatuzumab vedotin or MMAE; not warranted for the indication
“Carcinogenicity studies in animals have not been performed with polatuzumab vedotin or MMAE and are not warranted for the proposed indication.”
hERG / QT
MMAE hERG IC50 >100 µM (no appreciable inhibition)
“MMAE alone did not appreciably inhibit the human ether-à-go-go-related gene (hERG) channel (IC50 > 100 µM) in voltage-clamped human embryonic kidney cells”
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
Padcev
enfortumab vedotin · Nectin-4Not 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)