Datopotamab deruxtecan

FDA-approved

Datroway; Dato-DXd; DS-1062

Target

TROP-2 · TACSTD2

Sponsor

Daiichi Sankyo/AstraZeneca

Indication

TACSTD2+ breast/NSCLC

Target family

TACSTD / EpCAM-TROP

RP2D dose

6 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

6 adverse-event terms

Ocular

Any-grade

38%

G3+

3.4%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

24%

Express.

65.43%

Limbus

Express.

73.31%

Conjunctiva

Express.

86.39%

Lens

Express.

Retina / RPE

Express.

0 nTPM

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)

Reversibility

Reversible

Reported ocular events

Ocular toxicity (any ocular adverse reaction)38%

G3+ 3.4%n=1365

Keratitis26%

G3+ 6%n=319

Dry eye26%

G3+ 1.3%n=319

Lacrimation increased6%

n=1365

Conjunctivitis5%

n=1365

Blepharitis; Meibomian gland dysfunction; Blurred vision (named ocular PTs without quantified rate)-

n=1365

Per-trial detail

Adverse events by trial

BEGONIAPhase 1b/26 mg/kg (Dato) + 1120 mg durvalumab IV every 3 weeksn=62CTCAE NR (CT.gov serious/nonB

CT.gov NCT03742102 posted results (Other/non-serious AE module, all-cause, threshold 5%; MedDRA 26.0 & 27.1) NCT03742102 arm EG004 (Durvalumab + Dato-DXd); CT.gov AE module otherEvents

112 adverse-event terms · 22 systems · expand a system below

GI14

Stomatitis

69.35%G3+ 1.61%

43/62

Nausea

67.74%

42/62

Constipation

50%

31/62

Vomiting

29.03%G3+ 1.61%

18/62

Diarrhoea

16.13%

10/62

Abdominal pain

9.68%

6/62

Dry mouth

9.68%

6/62

Dyspepsia

9.68%

6/62

Gastrooesophageal reflux disease

6.45%

4/62

Haemorrhoids

6.45%

4/62

Gastritis

3.23%

2/62

Abdominal discomfort

1.61%

1/62

Abdominal pain upper

1.61%

1/62

Toothache

1.61%

1/62

Infections11

Investigations11

Dermatologic11

General8

Musculoskeletal8

Pulmonary7

Ocular6

Dry eye

27.42%

17/62

Keratitis

16.13%

10/62

Lacrimation increased

11.29%

7/62

Vision blurred

8.06%

5/62

Limbal stem cell deficiency

6.45%

4/62

Punctate keratitis

1.61%

1/62

Metabolic6

Neurologic (other)6

Hepatic3

Neoplasms3

Vascular3

Hematologic2

Endocrine2

Immune2

Injury2

Psychiatric2

Renal2

Cardiac1

Ear1

Other1

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

DXd

TopoI inhibitor

Linker structureC25H31N5O8

[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]

Payload structureC26H24FN3O6

CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)NC(=O)CO)O

Antibody

Antibody & Fc engineering

Antibody

datopotamab

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

0.74

Dev code

MAAP-9001a

Linker & conjugation

Linker chemistry

Linker profile

Linker

GGFG tetrapeptide

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

4.8 d

Cleavage trigger

Cathepsin B/L (GGFG tetrapeptide)

Release control

Conditional

Hydrophilicity mask

Hydrophilic-linker

Platform

DXd ADC platform

Formula

C25H31N5O8

Linker MW

529.55 Da

Linker TPSA

191.08 Å²

Linker xLogP

-1.3675

ADCdb linker

LIN0ECMCR

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

Payload

Payload & physicochemistry

Payload profile

Payload

DXd

Class

Topoisomerase I inhibitor

Mechanism

TopoI inhibitor

Released catabolite

DXd

Mechanistic subtype

TopoI

Stereochem / salt

Bystander

Yes

PAMPA rank

493.5 Da

XLogP3

logD₇.₄

1.4

TPSA

129 Å²

pKa

9.2 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C26H24FN3O6

PubChem CID

146160902

ADCdb payload

PAY0UXDSB

CAS no.

1599440-33-1

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

Dosing & regimen

Dosing

RP2D dose

6 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

360

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Pharmacology

Clinical pharmacokinetics

By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews

	Intact ADC	Total antibody	Free payload
Cmax	154µg/mL	—	2.8ng/mL
AUC	671µg*day/mL	—	18ng*day/mL
t½	4.8days	5.23days	5.5days
CL	0.6L/day	—	3L/h
Vd	3.5L+1	—	—

FDA label §12.3 Drugs@FDA reviewhover a value for dose / population / source · “+N” marks additional reported values

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

38 %

OAE grade 3+

3.4 %

OAE data status

reported

Severity (weighted)

13.8

Keratopathy

24 %

Conjunctival

Dry eye

27 %

Blurred vision

Dominant tissue

Ocular surface

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v5.0

Reversibility

Reversible

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

65.43 %

Cornea (limbal)

73.31 %

Conjunctiva

86.39 %

RPE

0 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v5Denominator: RP2D

Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort

6 mg/kg

IV every 3 weeks

38%

n=1365 · DATROWAY pooled all-indication safety (single agent 6 mg/kg)

6 mg/kg

Q3W (Day 1 of 21-day cycle)

26%

n=319 · TROPION-Breast02

6 mg/kg

Q3W (Day 1 of 21-day cycle)

24%

n=360 · TROPION-Breast01

6 mg/kg (Dato) + 1120 mg durvalumab

IV every 3 weeks

16.13%

n=62 · BEGONIA

6 mg/kg

IV every 3 weeks (21-day cycle)

16%

n=1365 · Pooled DATROWAY safety population

6 mg/kg

IV every 3 weeks

12%

n=125 · TROPION-Lung05/Lung01/PanTumor01 (pooled EGFR-mutated NSCLC)

6 mg/kg

IV every 3 weeks (21-day cycle)

12%

n=125 · TROPION-Lung05; TROPION-Lung01

6 mg/kg

IV every 3 weeks

11.94%

n=365 · TROPION-Breast01

6 mg/kg

IV every 3 weeks

7.5%

n=40 · DS1062a Chinese bridging (NSCLC/TNBC)

6 mg/kg

IV every 3 weeks

5.11%

n=137 · TROPION-Lung05

6 mg/kg

IV every 3 weeks

0.34%

n=299 · TROPION-Lung01

Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

Identity & registry

Identifiers, registry & notes

ADC id

datopotamab-deruxtecan

Approval status

FDA-approved

Approval year

2025

UniProt

P09758

ADCdb ADC

DRG0ZOYQV

ADCdb antibody

ANI0WKJOW

ADCdb target

TAR0MIBZW

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.