Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Korjuny: genotox, carcinogenicity and repro: done or skipped?
catumaxomab · EpCAM x CD3
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity studies have not been performed according to ICH S6(R1).”
Carcinogenicity
Not conducted (ICH S6); no proliferation of EpCAM+ or CD3+ cells in vitro
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”
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 (no relevant species; late-stage malignancy)
“Studies to investigate reproductive and developmental toxicity have not been performed due to the lack of an appropriate animal species, the intended patient population with late-stage malignant disease.”
Safety pharmacology
No dedicated studies; inferred from BiLu studies, human tissue cross-reactivity and in vitro hepatocytes
“Due to the restricted specificity of catumaxomab for human target antigens, safety aspects were assessed in vivo using the surrogate antibody BiLu in a secondary PD study and as part of a toxicology study (see Toxicology section).”
Genotox: Ames
Not conducted (ICH S6)
“Genotoxicity studies have not been performed according to ICH S6(R1).”
Genotox: in vitro mammalian
Not conducted (ICH S6)
“Genotoxicity studies have not been performed according to ICH S6(R1).”
Genotox: in vivo
Not conducted (ICH S6)
“Genotoxicity studies have not been performed according to ICH S6(R1).”
Carcinogenicity model
Not conducted (ICH S6); no proliferation of EpCAM+ or CD3+ tumour cells in vitro
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6. Catumaxomab does not have the potential to induce proliferation of EpCAM-positive or CD3-positive tumour cells (as demonstrated in 2° PD studies in vitro).”
Carcinogenicity timing
Not required (inappropriate for biotechnology-derived products per ICH S6)
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”
hERG / QT
Not conducted; no dedicated safety pharmacology endpoints; cardiovascular effects not expected (no heart tissue binding)
“Dedicated safety pharmacology endpoints were not included in these studies. However, catumaxomab is unlikely to affect the central nervous system as it is not expected to cross the blood-brain-barrier. Cardiovascular effects are not expected considering the lack of catumaxomab to human heart tissue in the tissue cross-reactivity study.”
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)
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))
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Not conducted (ICH S6(R1), ICH S9)