Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Columvi: which tox species, and why?
glofitamab · CD20 x CD3
Species
Cynomolgus monkey only
“The cynomolgus monkey is a relevant species for toxicology studies based on glofitamab binding to CD20 and CD3 on cynomolgus monkey B- and T-cells.”
Why that species
Comparable binding to human and monkey B- and T-cells (EC50 4.3/2.3 nM B, 21.1/13.2 nM T); no rodent, dog, minipig cross-reactivity
“Glofitamab bound to human and monkey B-cells with EC50 values of 4.3 and 2.3 nM respectively and bound to human and monkey T-cells with EC50 values of 21.1 and 13.2 nM respectively. This justified use of the cynomolgus monkey for general toxicology studies.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey (obinutuzumab pretreatment used in some studies)
“The cynomolgus monkey is a relevant species for toxicology studies based on glofitamab binding to CD20 and CD3 on cynomolgus monkey B- and T-cells.”
Species: general tox
Cynomolgus monkey only
“The Applicant conducted GLP studies in cynomolgus monkeys, including 2-week and 4-week repeat-dose toxicology studies, via the intravenous (IV) and subcutaneous (SC) routes.”
Species: DART
Not conducted; weight-of-evidence risk assessment (B-cell depletion, cytokine release)
“While no animal studies were conducted to assess the reproductive and developmental risks of glofitamab, a weight of evidence (WoE)-based risk assessment report was submitted.”
Species: carcinogenicity
Not conducted (advanced cancer, ICH S9)
“Glofitamab is intended for the treatment of patients with advanced cancer. In line with the ICH S9 guideline, no carcinogenicity studies were performed (ICH S9).”
Surrogate used in
No surrogate used; clinical molecule in cynomolgus monkey (obinutuzumab pretreatment in some studies)
“The cynomolgus monkey is a relevant species for toxicology studies based on glofitamab binding to CD20 and CD3 on cynomolgus monkey B- and T-cells.”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Chimpanzee (only relevant species, limited non-terminal studies) plus mouse with murine surrogate
Elrexfio
elranatamab · BCMA x CD3Cynomolgus monkey only
Epkinly
epcoritamab · CD20 x CD3Cynomolgus monkey only
Hemlibra
emicizumab · FIXa x FXCynomolgus monkey only
Imdelltra
tarlatamab · DLL3 x CD3Cynomolgus monkey (pivotal); mouse surrogate muS757 for EFD and 1-month study
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)No relevant species; in vitro human cell/tissue assays only
Korjuny
catumaxomab · EpCAM x CD3No relevant species; limited single-dose mouse, rat, one cynomolgus; BiLu mouse surrogate
Lunsumio
mosunetuzumab · CD20 x CD3Cynomolgus monkey only
Lynozyfic
linvoseltamab · BCMA x CD3Cynomolgus monkey only
Ordspono
odronextamab · CD20 x CD3Cynomolgus monkey only
Removab
catumaxomab · EpCAM x CD3No relevant species; in vitro human cells plus mouse surrogate (BiLu); limited single-dose rodent/monkey
Rybrevant
amivantamab · EGFR x METCynomolgus monkey only
Talvey
talquetamab · GPRC5D x CD3Cynomolgus monkey only (tool molecule for pivotal tox); no rodent tox
Tecvayli
teclistamab · BCMA x CD3Cynomolgus monkey only (rabbit used for SC local tolerance only)
Vabysmo
faricimab · VEGF-A x Ang-2Cynomolgus monkey only for pivotal tox (rabbit dropped after early studies)
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Cynomolgus monkey only