Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Ziihera: genotox, carcinogenicity and repro: done or skipped?
zanidatamab · HER2 x HER2 (biparatopic)
Genotoxicity
Not conducted (ICH S6(R1), ICH S9)
“Thus, mutagenicity studies are considered inappropriate and were not conducted.”
Carcinogenicity
Not conducted (ICH S9; advanced cancer, no mechanistic concern)
“Thus, given the intended patient population and lack of mechanistic concern, carcinogenicity studies are not planned with zanidatamab (ICH S9)”
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; weight-of-evidence, HER2 antibody class embryo-fetal toxicant (oligohydramnios)
“Consequently, the conduct of de novo developmental and reproductive toxicity (DART) studies is not warranted for zanidatamab.”
Safety pharmacology
Incorporated into 13-week monkey study (CV, respiratory, CNS); no effects
“Stand-alone safety pharmacology studies were not performed; however, appropriate safety assessments were included in the 13- week repeat-dose toxicology study”
Genotox: Ames
Not conducted (ICH S6(R1), ICH S9)
“Thus, mutagenicity studies are considered inappropriate and were not conducted.”
Genotox: in vitro mammalian
Not conducted (ICH S6(R1), ICH S9)
“Thus, mutagenicity studies are considered inappropriate and were not conducted.”
Genotox: in vivo
Not conducted (ICH S6(R1), ICH S9)
“Thus, mutagenicity studies are considered inappropriate and were not conducted.”
Carcinogenicity model
Not conducted (ICH S9; advanced cancer, no mechanistic concern)
“Thus, given the intended patient population and lack of mechanistic concern, carcinogenicity studies are not planned with zanidatamab (ICH S9)”
Carcinogenicity timing
Not required; FDA: carcinogenicity studies not warranted
“Carcinogenicity studies were not warranted.”
hERG / QT
No hERG assay; no cardiovascular effects in 13-week monkey study
“No test article-related adverse events were found in cardiovascular, respiratory, or central nervous system assessments.”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Not conducted (ICH S6(R1); protein of natural amino acids)
Columvi
glofitamab · CD20 x CD3Not conducted (ICH S6(R1))
Elrexfio
elranatamab · BCMA x CD3Not conducted (ICH S6(R1))
Epkinly
epcoritamab · CD20 x CD3Not conducted (ICH S6(R1), ICH S9)
Hemlibra
emicizumab · FIXa x FXNot conducted (ICH S6)
Imdelltra
tarlatamab · DLL3 x CD3Not conducted (ICH S6(R1))
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not conducted (fusion protein; ICH S6/S9)
Korjuny
catumaxomab · EpCAM x CD3Not conducted (ICH S6(R1))
Lunsumio
mosunetuzumab · CD20 x CD3Not conducted (ICH S6(R1))
Lynozyfic
linvoseltamab · BCMA x CD3Not conducted (antibody not expected to interact with DNA)
Ordspono
odronextamab · CD20 x CD3Not conducted (antibody not expected to interact with DNA)
Removab
catumaxomab · EpCAM x CD3Not conducted (not submitted; biologic, no relevant model)
Rybrevant
amivantamab · EGFR x METNot conducted (not appropriate for antibodies)
Talvey
talquetamab · GPRC5D x CD3Not conducted (ICH S6; biotechnology-derived product)
Tecvayli
teclistamab · BCMA x CD3Not conducted (ICH S6(R1))
Vabysmo
faricimab · VEGF-A x Ang-2Not conducted (ICH S6(R1))