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.”
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.”
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)