Enfortumab vedotin

FDA-approved

Padcev; ASG-22ME

Target

Nectin-4 · NECTIN4

Sponsor

Astellas/Seagen (Pfizer)

Indication

NECTIN4+ urothelial ca

Target family

Nectin / Ig-CAM

RP2D dose

1.25 mg/kg (max 125 mg)

D1+D8+D15 Q4WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

3 adverse-event terms

Ocular

Any-grade

40%

G3+

0.7%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

71.38%

Limbus

Express.

82.84%

Conjunctiva

Express.

56.73%

Lens

Express.

Retina / RPE

Express.

0.33%

0 nTPM

Dominant tissue

Ocular surface

Surface subtype

Conjunctival (on-target)

Reversibility

Reversible

Reported ocular events

Ocular disorders (any)40%

n=384

Dry eye24%

G3+ 0%n=440

Vision blurred10%

n=384

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Cleavable

3.8

DAR

Payload

MMAE

Tubulin inhibitor

Linker structureC28H40N6O7

[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H])c([H])c1[H]

Payload structureC39H67N5O7

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

AGS-22C3 (enfortumab)

Isotype

IgG1

Origin

Human

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

MC-vc-PAB (vedotin)

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric

DAR (mean)

3.8

DAR homogeneity

Heterogeneous

Plasma t½

3.6 d

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Stability note

acAb t½ 3.6 d in pooled urothelial PK; shorter than brentuximab (5 d) and tisotumab (4 d) reflecting weight-based dosing in obese urothelial population and higher CL

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE (free / unconjugated monomethyl auristatin E)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

Payload MMAE is a microtubule (tubulin polymerization) inhibitor. ADCdb in-vitro: enfortumab vedotin IC50 ~1.2-4.7 ng/mL on PC-3 prostate carcinoma and 37.8 ng/mL on T-47D breast carcinoma cells. Clinically FDA-approved Dec 2019 for advanced urothelial cancer.

Dosing & regimen

Dosing

RP2D dose

1.25 mg/kg (max 125 mg)

Schedule

D1+D8+D15 Q4W

Route

Fractionated

Yes

n at RP2D

384

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

40 %

OAE grade 3+

0.7 %

OAE data status

reported

Severity (weighted)

12.49

Keratopathy

Conjunctival

Dry eye

30 %

Blurred vision

10 %

Dominant tissue

Ocular surface

Surface subtype

Conjunctival (on-target)

Grading scale

CTCAE v4

Reversibility

Reversible

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

Cornea (central)

71.38 %

Cornea (limbal)

82.84 %

Conjunctiva

56.73 %

RPE

0.33 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

enfortumab-vedotin

Approval status

FDA-approved

Approval year

2019

UniProt

Q96NY8

ADCdb ADC

DRG0BBQSE

ADCdb antibody

ANI0LTVSQ

ADCdb target

TAR0MWTFE

Primary source

PADCEV HCP page; Dy 2024 Oncologist

Aliases & development codes

Padcev; ASG-22ME

Notes

Fractionated schedule reduces Cmax; surface-dominant mild OAE despite high NECTIN4 corneal expression. V3.1: oae_g3plus_pct=0.7 is DERIVED from Dy 2024 Oncologist; PADCEV label states 'No Grade 3-4 ocular toxicities reported' — value retained as C-tier derived estimate.