Korjuny
catumaxomab
Sources:EMA assessment report ↗
Species
no relevantMonkeyRatMouse
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No relevant species; limited single-dose mouse, rat, one cynomolgus; BiLu mouse surrogate
“None of the animal species analysed is suitable for assessing the safety of catumaxomab.”
Why that species
No binding to cells from rodents, rabbit, dog or NHPs; CD3/EpCAM binding human-specific
“None of the studies demonstrated binding of catumaxomab to cells from non-clinical species.”
Surrogate molecule
Yes: BiLu (anti-human EpCAM x anti-mouse CD3) in mice; only partially reflects catumaxomab
“Since BiLu recognises only murine CD3 but not murine EpCAM, the surrogate mAb only partially reflects the functionality of catumaxomab.”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“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.”
Route in tox
IV (maximal systemic exposure) and i.p. (clinical route); rabbit local tolerance multiple routes
“The intraperitoneal (i.p.) route of administration corresponds to the intended therapeutic use in humans.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity studies have not been performed according to ICH S6(R1).”
Carcinogenicity
Not conducted (ICH S6); no proliferation of EpCAM+ or CD3+ cells in vitro
“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”
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.”
Safety pharmacology
No dedicated studies; inferred from BiLu studies, human tissue cross-reactivity and in vitro hepatocytes
“Due to the restricted specificity of catumaxomab for human target antigens, safety aspects were assessed in vivo using the surrogate antibody BiLu in a secondary PD study and as part of a toxicology study (see Toxicology section).”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
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
“In this study, the no observed adverse effect level (NOAEL) for BiLu is considered to be the low dose (0.2 to 3.0 μg/kg).”
Risksopen answer page →
Immune & cytokine safety
In vitro TNF-α/IL-6/IL-2 release with EpCAM+ cells; transient lymphopenia (BiLu); neutralising HAMA/HARA
“In vitro data show that catumaxomab can induce the production of pro-inflammatory cytokines (e.g. TNF-α, IL-6 and IL-2) in the presence of EpCAM-expressing tumour cells.”
Biodistribution & persistence
123I-catumaxomab SCID xenograft: tumour peak 15.7% ID/g at 48 h; i.p. bioavailability 82%; mouse t1/2 128 h
“Tumour uptake of catumaxomab increased over the first 48 h and peaked at 15.7% ID/g; it then declined to 6.6% ID/g on Day 4.”
Modality-specific risk
Cytokine release and transient lymphopenia; liver (BiLu); on-target normal EpCAM tissue untestable; murine ADA
“Potential risks associated with the use of catumaxomab were identified in secondary PD studies, i.e. cytokine release that is enhanced in the presence of EpCAM-positive tumour cells and transient lymphopenia.”