Columvi
glofitamab · CD20 x CD3Monkey exposure below clinical: AUC multiples 0.03-0.28 in studies without obinutuzumab pretreatment
Blincyto: what safety margin did regulators accept?
blinatumomab · CD19 x CD3
Safety margin at NOAEL
Chimpanzee exposure (Cmax 0.9-1.36 ng/mL) higher than human Css at 9 and 28 µg/day; no NOAEL or multiple stated
“The exposure of chimpanzees in term of AUCinf was 2.9 (M) and 5.6 (F) ng.h/mL with Cmax of 0.9 (M) and 1.36 (F) ng/mL, i.e. higher than Css reached at the clinical doses of 9 µg/day (211 pg/mL) and 28 µg/day (621 pg/mL)”
NOAEL / key findings
No NOAEL assigned; lymphoid tissues target organs (lymphocyte depletion, decreased cellularity); chimp hypotension dose-limiting at 0.12 ug/kg
“Following daily administration of the surrogate for 4 or 13 weeks in mice, lymphoid tissues were the target organs of toxicity with decreased spleen weights and decreased cellularity or germinal center development observed in the lymph nodes, Peyer’s patches, and spleen.”
Same question, other bispecifics
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
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