Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Trodelvy: genotox, carcinogenicity and repro: done or skipped?
sacituzumab govitecan · Trop-2
Genotoxicity
Not conducted with ADC; SN-38 Ames negative, in vitro micronucleus positive (clastogenic)
“SN-38 was negative for mutagenicity in a bacterial reverse mutation (Ames) test but was clastogenic in the in vitro mammalian cell micronucleus test.”
Carcinogenicity
Not conducted (advanced cancer, ICH S9)
“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for 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
Not conducted (ICH S9); SN-38 genotoxic so embryo-fetal toxicity expected; female repro organ findings in monkey
“No embryo-fetal developmental toxicology studies were conducted or warranted to support this BLA submission, based on ICH S9.”
Safety pharmacology
Incorporated into repeat-dose monkey studies; no CNS, CV or respiratory findings; no hERG
“Safety pharmacology endpoints were assessed in the repeat-dose toxicity studies in monkeys. There were no sacituzumab govitecan-related findings on the central nervous, cardiovascular, or respiratory systems.”
Genotox: Ames
SN-38: negative in Ames assay
“SN-38 was negative for mutagenicity in a bacterial reverse mutation (Ames) test but was clastogenic in the in vitro mammalian cell micronucleus test.”
Genotox: in vitro mammalian
SN-38: positive (clastogenic) in in vitro mammalian cell micronucleus test
“SN-38 was negative for mutagenicity in a bacterial reverse mutation (Ames) test but was clastogenic in the in vitro mammalian cell micronucleus test.”
Genotox: in vivo
Not conducted (SN-38 genotoxicity assessed in vitro only)
“Genotoxic potential of SN-38 was assessed in vitro.”
Carcinogenicity model
Not conducted (advanced cancer indication)
“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for advanced cancer.”
Carcinogenicity timing
Not required for advanced cancer (ICH S9)
“No assessment of carcinogenicity has been conducted in accordance with ICH S9 according to which carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
hERG / QT
No CNS, cardiovascular (incl. QT/QTc) or respiratory effects in monkeys up to 120 mg/kg
“there were no apparent adverse effects on the CNS, the cardiovascular system including assessment of QT or corrected QT (QTc) interval or respiratory function following intravenous dosing of sacituzumab govitecan in cynomolgus monkeys at doses up to 120 mg/kg.”
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)
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)
Zynlonta
loncastuximab tesirine · CD19Not conducted with ADC; SG3199 clastogenic in vitro (micronucleus, chromosome aberration); Ames not assessable (cytotoxicity)