Tisotumab vedotin

FDA-approved

Tivdak; HuMax-TF-ADC

Target

Tissue factor (CD142) · F3

Sponsor

Genmab/Seagen

Indication

F3+ cervical cancer

Target family

Cytokine receptor

RP2D dose

2.0 mg/kg (max 200 mg)

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

13 adverse-event terms

Ocular

Any-grade

55%

G3+

3.3%

RP2D

sagittal schematic · Permanent

↳

Tissues shaded by reported adverse-event rate.

Cornea

17%

Express.

8.16%

Limbus

Express.

21.91%

Conjunctiva

38%

Express.

66.36%

Lens

Express.

Retina / RPE

Express.

51.39%

67.1 nTPM

Dominant tissue

Conjunctiva

Surface subtype

Conjunctival (on-target)

Reversibility

Permanent

Reported ocular events

Conjunctival adverse reactions37%

G3+ 0%n=101

Conjunctivitis32%

Dry eye29%

G3+ 0%n=101

Corneal adverse reactions21%

G3+ 3%n=101

Keratopathy17%

Periorbital adverse reactions16%

G3+ 0%n=101

Blepharitis5%

Ulcerative keratitis2.1%

Conjunctival ulcer1.4%

Corneal erosion0.9%

Conjunctival erosion0.5%

Symblepharon0.5%

Ulcerative keratitis, severe-

G3+ 1.2%

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Cleavable

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

tisotumab

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)

DAR homogeneity

Heterogeneous

Plasma t½

4.0 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

Median terminal t½ 4.04 d (range 2.26–7.25) — Gibiansky CPT-PSP 2022 popPK N=399 across 4 Ph1/2 trials; unconjugated MMAE t½ 2.56 d; weight-based CL covariate confirmed

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

Unconjugated (free) MMAE (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

ADCdb reports payload MMAE potency IC50 ~5 nM (HEL 92.1.7 cells, multidrug-resistance model); payload target is microtubules (MT). ADC clinical efficacy varies with tissue factor (F3/CD142) expression; cervical cancer Phase 2 ORR ~24%.

Dosing & regimen

Dosing

RP2D dose

2.0 mg/kg (max 200 mg)

Schedule

Q3W

Route

Fractionated

n at RP2D

425

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

55 %

OAE grade 3+

3.3 %

OAE data status

reported

Severity (weighted)

18.81

Keratopathy

17 %

Conjunctival

38 %

Dry eye

24 %

Blurred vision

Dominant tissue

Conjunctiva

Surface subtype

Conjunctival (on-target)

Grading scale

Unknown

Reversibility

Permanent

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

Cornea (central)

8.16 %

Cornea (limbal)

21.91 %

Conjunctiva

66.36 %

RPE

51.39 %

Retina (HPA)

67.1 nTPM

Cross-trial comparability

Ascertainment: Systematic eye examsScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

tisotumab-vedotin

Approval status

FDA-approved

Approval year

2021

UniProt

P13726

ADCdb ADC

DRG0PNJIT

ADCdb antibody

ANI0CBQNQ

ADCdb target

TAR0ZIMMG

Primary source

TIVDAK PI Section 6.1

Aliases & development codes

Tivdak; HuMax-TF-ADC

Notes

Conjunctival-dominant OAE tracks F3 conjunctival (66%) vs corneal (8%) expression ratio. V3.1: conjunctival AE 32→38% per updated TIVDAK pooled label (prev 32 was innovaTV 204-only).