Adcetris
brentuximab vedotin · CD30Conducted on MMAE: Ames and mouse lymphoma negative; rat micronucleus positive (aneugenic)
Decnupaz: genotox, carcinogenicity and repro: done or skipped?
pivekimab sunirine · CD123
Genotoxicity
Not conducted with ADC (ICH S9); FGN849 positive in Ames TA102, in vitro and in vivo micronucleus
“In accordance with ICH S9, genotoxicity studies have not been conducted with PVEK.”
Carcinogenicity
Not conducted (ICH S9)
“In accordance with ICH S9, carcinogenicity studies have not been conducted with PVEK.”
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 and FDA feedback); embryo-fetal harm expected from alkylating payload
“No reproductive and developmental studies have been conducted with PVEK, in accordance with ICH S9 and FDA feedback (Reference ID: 4704103).”
Safety pharmacology
Incorporated into GLP monkey studies (ECG, respiration); FGN849 hERG IC50 >1 µM; tremors at 0.1 mg/kg
“Stand-alone in vivo safety pharmacology studies were not conducted with PVEK or FGN849.”
Genotox: Ames
FGN849 payload: positive in Ames (strain TA102)
“Genotoxicity studies conducted with the FGN849 payload demonstrated positive results in the bacterial mutagenicity (Ames) assay (specifically in strain TA102), in vitro micronucleus assay in TK6 cells, and in vivo rat micronucleus assay, consistent with the DNA-alkylating mechanism of action.”
Genotox: in vitro mammalian
FGN849 payload: positive in in vitro micronucleus assay (TK6 cells)
“Genotoxicity studies conducted with the FGN849 payload demonstrated positive results in the bacterial mutagenicity (Ames) assay (specifically in strain TA102), in vitro micronucleus assay in TK6 cells, and in vivo rat micronucleus assay, consistent with the DNA-alkylating mechanism of action.”
Genotox: in vivo
FGN849 payload: positive in in vivo rat micronucleus assay
“Genotoxicity studies conducted with the FGN849 payload demonstrated positive results in the bacterial mutagenicity (Ames) assay (specifically in strain TA102), in vitro micronucleus assay in TK6 cells, and in vivo rat micronucleus assay, consistent with the DNA-alkylating mechanism of action.”
Carcinogenicity model
Not conducted (ICH S9)
“In accordance with ICH S9, carcinogenicity studies have not been conducted with PVEK.”
Carcinogenicity timing
Not required (ICH S9); none conducted
“In accordance with ICH S9, carcinogenicity studies have not been conducted with PVEK.”
hERG / QT
FGN849 payload hERG IC50 >1 µM
“The IC50 for the inhibitory effect of FGN849 on hERG potassium current was estimated to be greater than 1 µM.”
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
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)
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)