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Datopotamab deruxtecan FDA-approved Datroway; Dato-DXd; DS-1062
Sponsor
Daiichi Sankyo/AstraZeneca
Indication
TACSTD2+ breast/NSCLC
Target family
TACSTD / EpCAM-TROP
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
38%
Hepatic
24%
Neutrop.
30%
Thrombo.
-
Anemia
35%
GI
56%
ILD
2.4%
Neuro.
-
Also reported Other · 12 · 4 systems
6 adverse-event terms
Ocular Toxicity Target expression Compare
sagittal schematic · Reversible
↳ Tissues shaded by reported adverse-event rate.
Off-target signature
24% corneal toxicity, yet the TROP-2 target is detected in only 65.43% of central cornea - toxicity is not explained by target expression.
Dominant tissue
Ocular surface
Surface subtype
Corneal (off-target)
Reported ocular events
Ocular toxicity (any ocular adverse reaction) 38%
Blepharitis; Meibomian gland dysfunction; Blurred vision (named ocular PTs without quantified rate) -
02 Construct
Molecular anatomy Linker structure C25H31N5O8
[H]OC(=O)C([H])([H])N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])N([H])C(=O)C([H])([H])N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(=O)C([H])=C([H])C1=O)C([H])([H])c1c([H])c([H])c([H])c([H])c1[H] copy
Payload structure C26H24FN3O6
CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)NC(=O)CO)O copy
03 Antibody
Antibody & Fc engineering Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
DAR homogeneity
Heterogeneous
Cleavage trigger
Cathepsin B/L (GGFG tetrapeptide)
Release control
Conditional
Hydrophilicity mask
Hydrophilic-linker
In-vitro stability
>94%@21d/plasma
Stability note
Median elimination t½ 4.8 d (range 1.0–8.2) for Dato-DXd; released DXd t½ ~5.5 d. Same linker chemistry as T-DXd (1–2% DXd released at 21 d in plasma); shorter t½ than T-DXd reflects DAR 4 vs DAR 8 + datopotamab antibody PK
Class
Topoisomerase I inhibitor
Hydrophobicity · logD₇.₄
hydrophilic −2 +1.4 +4 lipophilic
Bioactivity note
DXd is a potent DNA topoisomerase I (TOP1) inhibitor (literature IC50 ~0.3 uM cell-free TOP1; ADCdb lists therapeutic target DNA topoisomerase 1 / PATR0EGDKN). ADCdb ADC entry reports clinical efficacy (ORR ~24-39% across NSCLC/TNBC cohorts) but no ADC binding constant or payload
07 Ocular & expression
Ocular profile & eye-tissue target expression Target profile → Dominant tissue
Ocular surface
Surface subtype
Corneal (off-target)
Target expression in eye tissues (HCA detection · HPA bulk)
Cross-trial comparability · source-verified
Ascertainment: Systematic eye exams Scale: CTCAE v5 Denominator: RP2D
08 Identity & registry
Identifiers, registry & notes ADC id
datopotamab-deruxtecan
Approval status
FDA-approved
Primary source
DATROWAY HCP; TROPION-Breast01 JCO 2024
Aliases & development codes
Datroway; Dato-DXd; DS-1062
Notes
V3.1: OAE values corrected to DATROWAY label pooled values (36% any, 2.2% G3+; prev 51/1.9 was TROPION-Breast01-specific subset). Severity ratio 0.06 after correction. Retains surface-dominant pattern.