Bizengri
zenocutuzumab · HER2 x HER3Mouse xenografts: HER2+ breast cancer (JIMT-1) and NRG1 fusion-positive lung and pancreatic patient-derived xenografts
Korjuny: animal efficacy model or human cells?
catumaxomab · EpCAM x CD3
Efficacy evidence
SCID mouse i.p. human ovarian carcinoma ascites xenograft treated with human PBMCs plus catumaxomab
“In vivo pharmacology of catumaxomab was investigated in a xenograft model of malignant ascites in immuno-deficient SCID mice. Mice received a human ovarian carcinoma xenograft i.p. and were treated one day later with human PBMCs (i.p.) together with a single i.p. injection of catumaxomab.”
Why that model
Catumaxomab does not react with murine CD3, so surrogate BiLu was used for syngeneic proof of concept
“Due to the lack of catumaxomab reactivity with murine CD3, the variant antibody BiLu (anti-human EpCAM & anti-mouse CD3) was used to demonstrate proof of concept in syngeneic mouse tumour models expressing human EpCAM.”
Reviewer's view of the efficacy data
EMA accepted a programme based on in vitro studies plus tailored in vivo work with catumaxomab and partially active surrogate BiLu
“Therefore, the nonclinical programme is based on in vitro studies and a tailored in vivo programme with catumaxomab and a surrogate mAb BiLu, that is cross-reactive with CD3 and therefore partially active in mice. This is accepted.”
Same question, other bispecifics
Blincyto
blinatumomab · CD19 x CD3Blinatumomab in NOD/SCID mouse tumor xenograft models
Columvi
glofitamab · CD20 x CD3Human HSC-engrafted NOG/NSG mice, non-tumor-bearing and tumor-bearing
Elrexfio
elranatamab · BCMA x CD3Multiple myeloma xenograft models (MM.1S, OPM2, MOLP8) with varying BCMA expression
Epkinly
epcoritamab · CD20 x CD3Human lymphoma cell line-derived xenograft (CDX) mouse models and one patient-derived xenograft (PDX) model
Hemlibra
emicizumab · FIXa x FXCynomolgus monkey models of acute and chronic hemophilia A
Imdelltra
tarlatamab · DLL3 x CD3Xenograft models in NSG mice injected with activated, expanded human T cells
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Mice engrafted with HLA-A*02:01/gp100+ Mel526 human melanoma cells plus human PBMCs; tumor growth inhibition
Lunsumio
mosunetuzumab · CD20 x CD3Human CD20/CD3 double-transgenic mice: peripheral and tissue B-cell depletion and T-cell activation (comparable to analogue 2H7v16/40G5c)
Lynozyfic
linvoseltamab · BCMA x CD3NSG mice co-implanted with human PBMC and NCI-H929 or MOLP-8 myeloma xenografts
Ordspono
odronextamab · CD20 x CD3Lymphoma tumour models in humanized (BRG) mice and immunodeficient NSG mice
Removab
catumaxomab · EpCAM x CD3Human ovarian carcinoma xenograft (catumaxomab); syngeneic human-EpCAM mouse tumour model with surrogate BiLu
Rybrevant
amivantamab · EGFR x METPatient-derived tumor xenografts with EGFR exon 20 insertion mutations in mice
Talvey
talquetamab · GPRC5D x CD3Myeloma cell line xenografts (H929 prophylactic; MM.1S, RPMI 8226 established) in humanized immunodeficient mice
Tecvayli
teclistamab · BCMA x CD3Human MM xenografts (H929, RPMI-8226) in human PBMC/T-cell-engrafted NSG mice
Vabysmo
faricimab · VEGF-A x Ang-2Laser-induced choroidal neovascularization (nAMD model) in cynomolgus monkeys, IVT faricimab vs ranibizumab
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)HER2 3+ xenografts in nude mice (SKOV-3, NCI-N87, patient-derived GXA 3054); no effect in HER2-negative model