Blincyto
blinatumomab · CD19 x CD3Chimpanzee exposure (Cmax 0.9-1.36 ng/mL) higher than human Css at 9 and 28 µg/day; no NOAEL or multiple stated
Lunsumio: what safety margin did regulators accept?
mosunetuzumab · CD20 x CD3
Safety margin at NOAEL
No NOAEL; CRS and infections in monkeys at exposures 0.008-1.84x human AUC
“When applying the corrections of AUC, estimations of exposure multiples resulted in values of 0.008 to 1.84, implying that CRS related effects and immunosuppression leading to infections occur at clinically relevant dose levels.”
NOAEL / key findings
No NOAEL; overall LOAEL 0.01 mg/kg (CRS effects at all doses); CNS perivascular infiltrates, liver, infections, one convulsion
“As CRS related effects were observed at all dose levels, a LOAEL was derived for all studies at the lowest dose levels resulting in an overall LOAEL of 0.01 mg/kg/day in cynomolgus monkeys.”
Same question, other bispecifics
Columvi
glofitamab · CD20 x CD3Monkey exposure below clinical: AUC multiples 0.03-0.28 in studies without obinutuzumab pretreatment
Elrexfio
elranatamab · BCMA x CD3Monkey NOAEL/LOEL 0.3 mg/kg exposure well below human exposure (0.1x or 0.2x)
Epkinly
epcoritamab · CD20 x CD3Monkey SC NOAEL 10 mg/kg: 5x clinical steady-state AUC; IV 1 mg/kg exposure equal to clinical AUC
Hemlibra
emicizumab · FIXa x FXMonkey NOAEL (30 mg/kg, 26-week) ~11x human AUC at 3 mg/kg QW
Korjuny
catumaxomab · EpCAM x CD3No margin: surrogate BiLu mouse NOAEL (0.2-3.0 µg/kg) equivalent to the clinical catumaxomab dose (1.43 µg/kg)
Rybrevant
amivantamab · EGFR x METMonkey AUC at 120 mg/kg 5x human AUC at the 1050 mg clinical dose
Tecvayli
teclistamab · BCMA x CD3Monkey NOEL 30 mg/kg IV weekly: 22x AUCtau, 48x Cmax vs human 1.5 mg/kg SC weekly
Vabysmo
faricimab · VEGF-A x Ang-2Ocular NOAEL 0.5 mg/eye (6-month monkey): exposure margin only around 1x human
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Monkey NOAEL 150 mg/kg: exposure ~10-fold above clinically relevant exposure
Bizengri
zenocutuzumab · HER2 x HER3Not stated in public reviews
Imdelltra
tarlatamab · DLL3 x CD3Not stated in public reviews
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not stated in public reviews
Lynozyfic
linvoseltamab · BCMA x CD3Not stated in public reviews
Ordspono
odronextamab · CD20 x CD3Not stated in public reviews
Removab
catumaxomab · EpCAM x CD3Not stated in public reviews
Talvey
talquetamab · GPRC5D x CD3Not stated in public reviews