Elahere
mirvetuximab soravtansine · FRαRationale not stated; FIH Study 0401 escalated from 0.15 mg/kg (TBW) to 7.0 mg/kg
Datroway: how was the first human dose set?
datopotamab deruxtecan · Trop-2
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
Monkey NOAEL 10 mg/kg for lung, cornea, skin, liver, thymus (intestinal toxicity at ≥10); rat NOAEL 20-60 mg/kg; ADA limits margins
“The NOAELs for pulmonary, corneal, dermal, hepatic, and lymphoid (thymic) toxicity was concluded to be 10 mg/kg.”
Same question, other ADCs
Enhertu
fam-trastuzumab deruxtecan · HER21/12 HED of monkey HNSTD (0.8 mg/kg), also matching minimum effective trough concentration
Kadcyla
ado-trastuzumab emtansine · HER2HNSTD-based: monkey HNSTD 10 mg/kg (q3w x4), below 1/10 rat severely toxic dose, used to set Phase I start
Zynlonta
loncastuximab tesirine · CD191/6 HNSTD in cynomolgus monkey cited as rationale for species choice; actual FIH calculation not detailed
Adcetris
brentuximab vedotin · CD30Not stated in public reviews
Besponsa
inotuzumab ozogamicin · CD22Not stated in public reviews
Decnupaz
pivekimab sunirine · CD123Not stated in public reviews
Emrelis
telisotuzumab vedotin · c-MetNot stated in public reviews
Mylotarg
gemtuzumab ozogamicin · CD33Not stated in public reviews
Padcev
enfortumab vedotin · Nectin-4Not stated in public reviews
Polivy
polatuzumab vedotin · CD79bNot stated in public reviews
Tivdak
tisotumab vedotin · Tissue factorNot stated in public reviews
Trodelvy
sacituzumab govitecan · Trop-2Not stated in public reviews