Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Imdelltra: genotox, carcinogenicity and repro: done or skipped?
tarlatamab · DLL3 x CD3
Genotoxicity
Not conducted (ICH S6(R1))
“Therefore, no genotoxicity studies have been conducted or are planned, consistent with ICH Harmonised Tripartite Guideline S6”
Carcinogenicity
Not conducted (ICH S9)
“No carcinogenicity studies have been conducted nor are any planned in accordance with ICH S9 (ICH, 2010).”
Reproductive & developmental
Mouse EFD study with surrogate muS757 (GD6, GD13): no maternal or EFD toxicity up to 4500 µg/kg; placental transfer; no fertility studies
“Two administrations of a tarlatamab surrogate, mus757, that binds mouse CD3 and DLL3, to pregnant mice on gestational days (GD) 6 and GD 13 did not result in maternal toxicity or embryo-fetal development toxicity at doses ≤4500 µg/kg.”
Safety pharmacology
Incorporated into monkey tox studies (ECG, respiratory rate, body temperature, neurologic exams)
“Electrocardiographic assessments, respiratory rate, body temperature measurements, and neurologic examinations were included on the toxicology studies in the cynomolgus monkey”
Same question, other bispecifics
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)
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)