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
Rybrevant: what safety margin did regulators accept?
amivantamab · EGFR x MET
Safety margin at NOAEL
Monkey AUC at 120 mg/kg 5x human AUC at the 1050 mg clinical dose
“Exposures achieved in monkeys at the 120 mg/kg dose level were 5x1 times higher than the AUC in patients (102954 µg*h/mL) at the once weekly dose for 4 weeks, then every 2 weeks clinical dose of 1050 mg.”
NOAEL / key findings
NOAEL 120 mg/kg/wk (highest dose; >=5.3x human AUC); minimal liver, kidney, stomach findings
“The no-observed-adverse-effect level (NOAEL) in the toxicology studies was 120 mg/kg/week (highest tested dose) for the 6-week and 3-month toxicity GLP studies.”
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)
Lunsumio
mosunetuzumab · CD20 x CD3No NOAEL; CRS and infections in monkeys at exposures 0.008-1.84x human AUC
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