Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Columvi: genotox, carcinogenicity and repro: done or skipped?
glofitamab · CD20 x CD3
Genotoxicity
Not conducted (ICH S6(R1))
“genotoxicity studies have not been conducted with glofitamab. It is not expected that glofitamab would interact directly with DNA or other chromosomal material.”
Carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies with glofitamab have not been conducted and are not planned. Glofitamab is intended for the treatment of patients with 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 (weight-of-evidence assessment; B-cell depletion and cytokine release risk to pregnancy)
“While no animal studies were conducted to assess the reproductive and developmental risks of glofitamab, a weight of evidence (WoE)-based risk assessment report was submitted.”
Safety pharmacology
Incorporated into repeat-dose monkey studies (CNS, respiratory, CV); cytokine-related heart rate increase
“No specific safety pharmacology studies have been conducted with glofitamab. Effects on the central nervous, respiratory, and cardiovascular systems were evaluated in repeat-dose toxicity studies in cynomolgus monkeys.”
Genotox: Ames
Not conducted (ICH S6)
“(ICH S6[R1] 2011), genotoxicity studies have not been conducted with glofitamab.”
Genotox: in vitro mammalian
Not conducted (ICH S6)
“(ICH S6[R1] 2011), genotoxicity studies have not been conducted with glofitamab.”
Genotox: in vivo
Not conducted (ICH S6)
“(ICH S6[R1] 2011), genotoxicity studies have not been conducted with glofitamab.”
Carcinogenicity model
Not conducted (advanced cancer, ICH S9)
“Glofitamab is intended for the treatment of patients with advanced cancer. In line with the ICH S9 guideline, no carcinogenicity studies were performed (ICH S9).”
Carcinogenicity timing
Not required: advanced cancer indication (ICH S9)
“Glofitamab is intended for the treatment of patients with advanced cancer. In line with the ICH S9 guideline, no carcinogenicity studies were performed (ICH S9).”
hERG / QT
No hERG assay; monkey ECG showed no effect on QRS or QTc (cytokine-related heart rate increase only)
“There was no effect of glofitamab administration on QRS duration or corrected QTc interval.”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Not conducted (ICH S6(R1); protein of natural amino acids)
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))
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Not conducted (ICH S6(R1), ICH S9)