Bizengri
zenocutuzumab · HER2 x HER3Mouse xenografts: HER2+ breast cancer (JIMT-1) and NRG1 fusion-positive lung and pancreatic patient-derived xenografts
Talvey: animal efficacy model or human cells?
talquetamab · GPRC5D x CD3
Efficacy evidence
Myeloma cell line xenografts (H929 prophylactic; MM.1S, RPMI 8226 established) in humanized immunodeficient mice
“The in vivo antitumor activity of talquetamab was evaluated in cell line-derived xenograft (CDX) mouse models. These studies evaluated the prevention of tumorigenesis in a prophylactic model (H929 cell line) and tumor growth inhibition (TGI) in established tumor models (MM.1S and RPMI 8226 cell lines).”
Why that model
No binding to murine CD3, so efficacy mice were humanized with human PBMCs or T-cells
“Talquetamab does not bind murine CD3; therefore, the CDX studies were conducted in immunodeficient mice that were humanized by intravenous (IV) implantation of human peripheral blood mononuclear cells (PBMCs) or human T-cells.”
Reviewer's view of the efficacy data
EMA: xenograft studies gave in vivo proof of concept despite failure in the second therapeutic model
“Although talquetamab failed in second therapeutic xenograft tumour model (other MM origin cells and use of human pan T-cell implantation), these studies provided the proof of concept for in vivo functionality for this bi-specific Mab.”
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
Korjuny
catumaxomab · EpCAM x CD3SCID mouse i.p. human ovarian carcinoma ascites xenograft treated with human PBMCs plus catumaxomab
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
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