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
Removab: 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 Removab 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: No NOAEL for catumaxomab; no acute toxicity at high single doses; surrogate BiLu suggested liver toxicity (EMA assessment report, p. 16)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No repeat-dose toxicology study (no relevant species)
“The most notable consequence of the inability to find a relevant species is that the present application does not contain repeated dose toxicology studies of catumaxomab.”
Pivotal GLP studies
No repeat-dose studies; single-dose catumaxomab in mice, rats, one cynomolgus; BiLu single-dose mouse; rabbit local tolerance
“In the few studies performed in rats, mice and one cynomolgus monkey, no acute toxicity was seen even at very high doses of catumaxomab.”
DART package
Species: DART
Not conducted (not submitted)
“Reproductive and developmental toxicity studies have not been submitted.”
Reproductive & developmental
Not conducted (not submitted)
“Reproductive and developmental toxicity studies have not been submitted.”
PPND / ePPND: when
Not conducted: reproductive and developmental toxicity studies not submitted
“Reproductive and developmental toxicity studies have not been submitted.”
Carcinogenicity
Species: carcinogenicity
Not conducted (not submitted)
“Carcinogenicity studies have not been submitted.”
Carcinogenicity model
Not conducted (not submitted)
“Carcinogenicity studies have not been submitted.”
Carcinogenicity timing
Not required: absence of studies accepted given no suitable animal models
“The absence of many nonclinical studies is considered acceptable for an antibody, given the absence of suitable animal models.”
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
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
Vabysmo
faricimab · VEGF-A x Ang-2Not stated in public reviews