Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Lunsumio: genotox, carcinogenicity and repro: done or skipped?
mosunetuzumab · CD20 x CD3
Genotoxicity
Not conducted (ICH S6(R1))
“In accordance with the current ICH guidance (ICH S6(R1) 2011), genotoxicity studies have not been conducted with mosunetuzumab because the potential of biotechnology products, in particular high molecular weight monoclonal antibodies, to elicit DNA damage in somatic or germ cells via electrophilic reactions is unlikely.”
Carcinogenicity
Not conducted (ICH S6R1, oncology indication)
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
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 (dedicated DART); NHP EFD/PPND waived on weight of evidence; no reproductive organ effects in 26-week monkey study
“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993).”
Safety pharmacology
Incorporated into GLP single-dose (telemetry CV) and repeat-dose monkey studies
“Cardiovascular effects were investigated as part of the single dose GLP study in monkeys (Study 14- 1246).”
Genotox: Ames
Not conducted (ICH S6(R1))
“In accordance with the current ICH guidance (ICH S6(R1) 2011), genotoxicity studies have not been conducted with mosunetuzumab because the potential of biotechnology products, in particular high molecular weight monoclonal antibodies, to elicit DNA damage in somatic or germ cells via electrophilic reactions is unlikely.”
Genotox: in vitro mammalian
Not conducted (ICH S6(R1))
“In accordance with the current ICH guidance (ICH S6(R1) 2011), genotoxicity studies have not been conducted with mosunetuzumab because the potential of biotechnology products, in particular high molecular weight monoclonal antibodies, to elicit DNA damage in somatic or germ cells via electrophilic reactions is unlikely.”
Genotox: in vivo
Not conducted (ICH S6(R1))
“In accordance with the current ICH guidance (ICH S6(R1) 2011), genotoxicity studies have not been conducted with mosunetuzumab because the potential of biotechnology products, in particular high molecular weight monoclonal antibodies, to elicit DNA damage in somatic or germ cells via electrophilic reactions is unlikely.”
Carcinogenicity model
Not conducted (oncology indication, ICH S6(R1))
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
Carcinogenicity timing
Not required; none conducted or planned for the oncology indication
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
hERG / QT
No hERG; monkey telemetry: heart-rate-dependent PR/QT shortening, no QTc change vs pre-dose
“When corrected for heart-rate, no significant differences were noted in the QT intervals (QTc) compared with pre-dose levels. It appears that effects on QT were heart-rate dependent and not indicative of an effect of mosunetuzumab on ventricular repolarization kinetics, which is accepted.”
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))
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)