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
Kimmtrak: how was the first human dose set?
tebentafusp · CD3 x gp100 (TCR fusion)
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Kimmtrak 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 (no animal tox); in vitro reactivity vs melanocytes at 10-100 pM, loss of specificity from 1 nM (FDA multi-discipline review, p. 41)
NOAEL / key findings
No NOAEL (no animal tox); in vitro reactivity vs melanocytes at 10-100 pM, loss of specificity from 1 nM
“Tebentafusp demonstrated broad loss of specificity for the target pHLA complex from 1 nM (1,000× MABEL), where consistent evidence of T cell activation (IFNγ release) and/or redirected killing (GrB release) was observed across the different normal cells tested.”
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
Imdelltra
tarlatamab · DLL3 x CD3Not 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