Lunsumio
mosunetuzumab · CD20 x CD3US, Republic of Korea, Canada: dose-escalation part (Group A) of study GO29781 in patients with R/R B-cell NHL
Columvi: what was done before first-in-human, and what came after?
glofitamab · CD20 x CD3
Before first-in-human
First-in-human: where
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Repeat-dose tox before first-in-human
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
First-in-human starting dose
MABEL: monkey PK/PD IL-6 excursion model plus in vitro human/monkey whole-blood cytokine data; 5 ug flat dose
“A pharmacokinetic-pharmacodynamic (PK/PD) model for cytokine excursions in cynomolgus monkeys, particularly interleukin 6 (IL-6), was built and translated to humans. The human starting dose was selected to keep the predicted IL-6 excursion below a predefined threshold in patients”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
4-week IV/SC step-up cynomolgus monkey study with 4-week treatment-free period
“RO7082859: A 4-week intravenous and subcutaneous toxicity and toxicokinetic study in Mauritius cynomolgus monkeys followed by a 4-week treatment-free period”
Pivotal GLP studies
GLP cynomolgus 2-week IV (2 weekly doses) and 4-week IV/SC step-up (every other day) studies with recovery
“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.”
DART package
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.”
Reproductive & developmental
Not conducted (weight-of-evidence assessment; B-cell depletion and cytokine release risk to pregnancy)
“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.”
PPND / ePPND: when
No PPND or other reproductive animal studies; weight-of-evidence risk assessment instead
“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.”
Carcinogenicity
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).”
Carcinogenicity model
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).”
Carcinogenicity timing
Not required: advanced cancer indication (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).”
Same question, other multispecifics
Rybrevant
amivantamab · EGFR x METUS and ex-US (Australia, Canada, China, France, Japan, Korea, Spain, Taiwan, UK): first-in-human dose escalation/expansion in advanced NSCLC
Talvey
talquetamab · GPRC5D x CD3US and ex-US (Belgium, France, Germany, Israel, Netherlands, Poland, Korea, Spain): first-in-human dose escalation/expansion
Tecvayli
teclistamab · BCMA x CD3US and ex-US (Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, UK): first-in-human study
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)North America and South Korea: first-in-human study ZWI-ZW25-101 in HER2-expressing cancers
Bizengri
zenocutuzumab · HER2 x HER3Not stated in public reviews
Blincyto
blinatumomab · CD19 x CD3Not stated in public reviews
Elrexfio
elranatamab · BCMA x CD3Not stated in public reviews
Epkinly
epcoritamab · CD20 x CD3Not stated in public reviews
Hemlibra
emicizumab · FIXa x FXNot 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
Korjuny
catumaxomab · EpCAM x CD3Not 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
Vabysmo
faricimab · VEGF-A x Ang-2Not stated in public reviews