Enhertu
fam-trastuzumab deruxtecan · HER2Japan and US: multicenter first-in-human study (Study DS8201-A-J101)
Elahere: what was done before first-in-human, and what came after?
mirvetuximab soravtansine · FRα
Before first-in-human
First-in-human: where
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.
Repeat-dose tox before first-in-human
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.
First-in-human starting dose
Rationale not stated; FIH Study 0401 escalated from 0.15 mg/kg (TBW) to 7.0 mg/kg
“MIRV: Dose escalation: 0.15 mg/kg TBW to 7.0 mg/kg TBW (n = 44 Q3W; n = 25 QW)”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
10-week cynomolgus monkey IV study (every 3 weeks, 4 doses) with 5-week recovery
“IMGN853 at doses of 0, 2, 4, and 8 mg/kg/dose was administered intravenously (slow push) to cynomolgus monkeys once every 3 weeks for up to 10 weeks (a total of 4 doses) with a 5- week recovery period (n=6/sex/group).”
Pivotal GLP studies
10-week GLP monkey (2, 4, 8 mg/kg q3w IV, 5-week recovery); single-dose monkey; GLP rabbit ocular 4-week weekly and 12-week q3w
“IMGN853 at doses of 0, 2, 4, and 8 mg/kg/dose was administered intravenously (slow push) to cynomolgus monkeys once every 3 weeks for up to 10 weeks (a total of 4 doses) with a 5- week recovery period (n=6/sex/group).”
DART package
Species: DART
Not conducted
“No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine.”
Reproductive & developmental
Not conducted (ICH S9); DM4 genotoxic, embryotoxicity expected; FRα mutations linked to birth defects
“No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine.”
PPND / ePPND: when
Not conducted: no reproductive or developmental studies (DM4 genotoxic, toxic to dividing cells)
“No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine. The cytotoxic component of ELAHERE, DM4, disrupts microtubule function, is genotoxic, and can be toxic to actively dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.”
Carcinogenicity
Species: carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not needed to support the advanced cancer indication, consistent with ICH S9 guidance.”
Carcinogenicity model
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not needed to support the advanced cancer indication, consistent with ICH S9 guidance.”
Carcinogenicity timing
Not required for the advanced cancer indication (ICH S9)
“Carcinogenicity studies were not needed to support the advanced cancer indication, consistent with ICH S9 guidance.”
Same question, other ADCs
Adcetris
brentuximab vedotin · CD30Not stated in public reviews
Besponsa
inotuzumab ozogamicin · CD22Not stated in public reviews
Datroway
datopotamab deruxtecan · Trop-2Not stated in public reviews
Decnupaz
pivekimab sunirine · CD123Not stated in public reviews
Emrelis
telisotuzumab vedotin · c-MetNot stated in public reviews
Kadcyla
ado-trastuzumab emtansine · HER2Not 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
Zynlonta
loncastuximab tesirine · CD19Not stated in public reviews