Adcetris
brentuximab vedotin · CD30Monkey NOAEL serum exposure ~2 to 3x human exposure at the clinical dose
Emrelis: what safety margin did regulators accept?
telisotuzumab vedotin · c-Met
Safety margin at NOAEL
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.
NOAEL / key findings
13-week cyno: no adverse findings to 3 mg/kg; 4-week: neutropenia/marrow at ≥6 mg/kg, ovary/uterus ≥3 mg/kg, eye, thymus
“Myelosuppression occurred at the middle and high doses, which correlated histologically with decreased bone marrow cellularity.”
Same question, other ADCs
Besponsa
inotuzumab ozogamicin · CD22No NOAEL for rat male reproductive effects, seen at ~0.3x human AUC
Datroway
datopotamab deruxtecan · Trop-2Monkey NOAEL 10 mg/kg (lung, cornea, skin, liver, thymus): margin of exposure 0.25 (below human exposure)
Decnupaz
pivekimab sunirine · CD123No NOAEL in 13-week monkey study: thymic atrophy at the lowest dose (0.01 mg/kg)
Elahere
mirvetuximab soravtansine · FRαMonkey NOAEL 4 mg/kg: AUC margin 0.09 (AUC0-24 vs AUCtau) to 0.57 (AUC0-∞)
Enhertu
fam-trastuzumab deruxtecan · HER2Monkey 30 mg/kg (3-month study) ≥7x human AUC at 5.4 mg/kg
Kadcyla
ado-trastuzumab emtansine · HER2Monkey HNSTD 10 mg/kg (2040 µg DM1/m2) approximately equivalent to the clinical dose
Padcev
enfortumab vedotin · Nectin-4Monkey ~3-fold and rat (MTD) ~2-fold human systemic exposure at recommended dose
Tivdak
tisotumab vedotin · Tissue factorMonkey HNSTD 3 mg/kg ~1.35-2.56x human exposure (Cmax and AUC)
Trodelvy
sacituzumab govitecan · Trop-2Monkey NOAEL/HNSTD 50 mg/kg: 6.4x (total antibody), 4.6x (total SN-38), 3.1x (free SN-38) human exposure at 10 mg/kg
Zynlonta
loncastuximab tesirine · CD19Monkey 0.3 mg/kg ~3x human AUC at MRHD 0.15 mg/kg
Mylotarg
gemtuzumab ozogamicin · CD33Not stated in public reviews
Polivy
polatuzumab vedotin · CD79bNot stated in public reviews