Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Lynozyfic: genotox, carcinogenicity and repro: done or skipped?
linvoseltamab · BCMA x CD3
Genotoxicity
Not conducted (antibody not expected to interact with DNA)
“No genotoxicity studies were conducted with linvoseltamab as antibodies are not expected to interact directly with DNA or other chromosomal material.”
Carcinogenicity
Not conducted (ICH S9, advanced malignancy)
“As linvoseltamab is intended for use in patients with advanced malignancies, carcinogenicity studies were not conducted with linvoseltamab, consistent with ICH S9 guideline Nonclinical Evaluation of Anticancer Pharmaceuticals.”
Reproductive & developmental
Not conducted; weight-of-evidence (T-cell activation, cytokine release, B-cell depletion, placental IgG transfer)
“The Applicant provided a weight of evidence (WOE)-based risk assessment to assess the potential for reproductive and developmental toxicities.”
Safety pharmacology
Incorporated into 5-week GLP monkey study (telemetry ECG, BP, respiration, CNS); no effects to 10 mg/kg/week
“Safety pharmacology evaluations were integrated into a GLP-compliant repeat-dose toxicology study conducted in Cynomolgus monkeys using linvoseltamab (R5458-TX-17179, also see Repeat dose toxicity).”
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)
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))
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)