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
Korjuny: what was done before first-in-human, and what came after?
catumaxomab · EpCAM 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
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Korjuny don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for multispecifics
ADCs with cytotoxic payloads follow the S9 rules (1/10 STD10 or 1/6 HNSTD of the ADC, scaled by body surface area). For immune agonists, a MABEL-based start dose should be considered instead.
“For example, for cytotoxic payloads, the starting clinical dose can be determined using either 1/10th the Severely Toxic Dose (STD) in 10% of animals (STD10) in rodents or 1/6th the Highest Non- Severely Toxic Dose (HNSTD) in non-rodents, for the ADC based on body surface area, depending on which is the most appropriate and/or sensitive species.”
This product's starting point
NOAEL / key findings: BiLu NOAEL 0.2-3.0 µg/kg (~clinical dose); liver, mammary, spleen, marrow, lymphocyte findings; catumaxomab tolerated 1.5 mg/kg mouse, 0.5 mg/kg rat (EMA assessment report, p. 38)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No repeat-dose toxicity study (no appropriate animal species); single/escalating-dose studies only
“Repeat-dose toxicity studies have not been performed with catumaxomab due to the lack of an appropriate animal species.”
Pivotal GLP studies
GLP single-dose IV: mouse, rat, one cyno (escalating 1-300 µg/kg); BiLu 4-dose escalating mouse; rabbit local tolerance
“Therefore, a limited toxicology programme was performed, i.e. single dose toxicity studies with catumaxomab in mice, rats and cynomolgus.”
DART package
Species: DART
Not conducted (no appropriate species; late-stage malignancy)
“Studies to investigate reproductive and developmental toxicity have not been performed due to the lack of an appropriate animal species, the intended patient population with late-stage malignant disease.”
Reproductive & developmental
Not conducted (no relevant species; late-stage malignancy)
“Studies to investigate reproductive and developmental toxicity have not been performed due to the lack of an appropriate animal species, the intended patient population with late-stage malignant disease.”
PPND / ePPND: when
No PPND or other DART studies: no appropriate species, late-stage malignancy population
“Studies to investigate reproductive and developmental toxicity have not been performed due to the lack of an appropriate animal species, the intended patient population with late-stage malignant disease.”
Carcinogenicity
Species: carcinogenicity
Not conducted (ICH S6)
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”
Carcinogenicity model
Not conducted (ICH S6); no proliferation of EpCAM+ or CD3+ tumour cells in vitro
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6. Catumaxomab does not have the potential to induce proliferation of EpCAM-positive or CD3-positive tumour cells (as demonstrated in 2° PD studies in vitro).”
Carcinogenicity timing
Not required (inappropriate for biotechnology-derived products per ICH S6)
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”
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
Columvi
glofitamab · CD20 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
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