Columvi
glofitamab · CD20 x CD3MABEL: monkey PK/PD IL-6 excursion model plus in vitro human/monkey whole-blood cytokine data; 5 ug flat dose
Imdelltra: how was the first human dose set?
tarlatamab · DLL3 x CD3
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Imdelltra 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: HNSTD 4500 µg/kg (maximum feasible dose); lymphocyte decreases, transient heart rate increase, pituitary mononuclear infiltrates (FDA multi-discipline review, p. 65)
NOAEL / key findings
HNSTD 4500 µg/kg (maximum feasible dose); lymphocyte decreases, transient heart rate increase, pituitary mononuclear infiltrates
“Tarlatamab-related changes are reversible and clinically monitorable, and the highest non-severely toxic dose was determined to be 4500 µg/kg based on the absence of any tarlatamab-related adverse findings.”
Same question, other multispecifics
Lunsumio
mosunetuzumab · CD20 x CD3MABEL-type: EC20 from in vitro human PBMC cytokine release / T-cell activation assay
Vabysmo
faricimab · VEGF-A x Ang-2Starting dose 0.5 mg/eye IVT supported by monkey tox data (6 mg/eye high dose not initially supported; dose escalation gated)
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
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
Rybrevant
amivantamab · EGFR x METNot stated in public reviews
Talvey
talquetamab · GPRC5D x CD3Not stated in public reviews
Tecvayli
teclistamab · BCMA x CD3Not stated in public reviews
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Not stated in public reviews