Nonclinical precedent Request an invite
Precedia/Antibody-drug conjugates/Tivdak/Flexibility

Tivdak: what flexibility did regulators accept, and why?

tisotumab vedotin · Tissue factor
Check my plan vs. these
Flexibility accepted
DARTVerdict not stated
No embryo-fetal development study with the ADC; rat EFD study of the MMAE payload (from brentuximab vedotin) relied on
Why: MMAE payload EFD study in rats, previously reviewed for brentuximab vedotin
“Dedicated embryo-fetal developmental toxicity studies were not conducted with tisotumab vedotin. However, MMAE (SGD-1010) was evaluated in rats as part of a GLP embryo-fetal developmental and TK study that was initially reviewed by the FDA under BLA 125388 for brentuximab vedotin.”
✓ VerifiedFDA multi-discipline review, p. 57Source ↗

Same question, other ADCs

Adcetris

brentuximab vedotin · CD30
Exposure ratios derived from single-dose studies and a different dosing scheme rather than repeat-dose data matching the clinical regimen

Besponsa

inotuzumab ozogamicin · CD22
No pharmacologically relevant toxicology species: antibody does not bind rat or monkey CD22, so only target-independent payload toxicity assessed

Datroway

datopotamab deruxtecan · Trop-2
No fertility, embryo-fetal or pre- and postnatal development studies; fertility assessed from repeat-dose studies

Decnupaz

pivekimab sunirine · CD123
No pharmacologically relevant toxicology species: no CD123 cross-reactivity in mouse, rat or cynomolgus monkey; monkey studies assess off-target and payload toxicity only

Elahere

mirvetuximab soravtansine · FRα
No reproductive or developmental toxicity studies at all, including embryo-fetal development

Emrelis

telisotuzumab vedotin · c-Met
No fertility, embryo-fetal or pre/postnatal development studies with the ADC; MMAE payload EFD data relied on

Enhertu

fam-trastuzumab deruxtecan · HER2
No embryo-fetal development or other reproductive toxicity studies with the ADC

Kadcyla

ado-trastuzumab emtansine · HER2
No embryo-fetal development studies with the ADC

Mylotarg

gemtuzumab ozogamicin · CD33
No pharmacologically relevant species: antibody does not bind monkey CD33 or rat and monkey tissues; toxicity studies address off-target effects only

Padcev

enfortumab vedotin · Nectin-4
Chronic (13-week) toxicity in rat only; monkey limited to 4 weeks

Polivy

polatuzumab vedotin · CD79b
Polatuzumab does not bind monkey CD79b; target-mediated toxicity assessed with a surrogate ADC binding monkey CD79b

Trodelvy

sacituzumab govitecan · Trop-2
No embryo-fetal development or fertility studies; genotoxic SN-38 payload assumed teratogenic

Zynlonta

loncastuximab tesirine · CD19
No pharmacologically relevant species; CD19-mediated toxicity could not be evaluated in any nonclinical species

Summary across all 14 ADCs →