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%

Per-trial detail

Adverse events by trial

innovaTV 204 (NCT03438396) — pivotal cervicalPhase 22.0 mg/kg IV once every 3 weeks (Day 1 of 21-day cycle)n=101CTCAE 4.03RP2DB

ClinicalTrials.gov posted results — NCT03438396 (Tisotumab Vedotin) [4/101] NCT03438396

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

Ocular34

Dry eye

24.8%

25/101

Keratitis

10.9%

11/101

Blepharitis

6.9%

7/101

Punctate keratitis

5.9%

6/101

Ocular hyperaemia

4/101

Lacrimation increased

4/101

Vision blurred

3/101

Meibomianitis

3/101

Eye discharge

3/101

Entropion

3/101

Cataract

2/101

Conjunctival haemorrhage

2/101

Trichiasis

2/101

Corneal erosion

2/101

Conjunctival hyperaemia

2/101

Amblyopia

1/101

Asthenopia

1/101

Blepharospasm

1/101

Chalazion

1/101

Conjunctival erosion

1/101

Retinal exudates

1/101

Photophobia

1/101

Ocular hypertension

1/101

Noninfective conjunctivitis

1/101

Meibomian gland dysfunction

1/101

Keratopathy

1/101

Foreign body sensation in eyes

1/101

Eye pruritus

1/101

Eye pain

1/101

Eye movement disorder

1/101

Eye irritation

1/101

Eye inflammation

1/101

Corneal scar

1/101

Corneal bleeding

1/101

GI28

Infections25

Investigations20

General18

Musculoskeletal16

Pulmonary14

Dermatologic14

Metabolic13

Neurologic (other)13

Injury11

Other10

Renal8

Vascular7

Hematologic6

Psychiatric4

Cardiac3

Ear2

Endocrine2

Hepatic2

Neoplasms2

Immune1

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

Target KD (nM)

153

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

Plasma protein binding (%)

68 %

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

ADA rate (%)

5.7 %

Pharmacology

Clinical pharmacokinetics

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

	Intact ADC	Free payload
Cmax	40.8 (SD 8.12)ug/mL+1	5.91 (SD 4.2)ng/mL+1
AUC	57.5 (SD 13.4) [AUC0-21d / AUCtau, day 0-21]day*ug/mL+1	50 (SD 35.8) [AUC0-21d / AUCtau, day 0-21]day*ng/mL+1
Tmax	near end of infusion (30-min IV infusion)	approximately 2 to 3 (peak after dosing)days+1
t½	4.04 (range 2.26-7.25) [terminal, median]days	2.56 (range 1.81-4.10) [terminal, median]days
CL	1.54 (%CV 28.8) [linear clearance]L/day+1	45.9 (%CV 61.1) [linear clearance; elimination rate-limited by release from ADC]L/day
Vd	7.83 (%CV 19.1) [steady-state volume, Vss]L+2	—

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

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

CTCAE v5.0

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 · source-verified

Ascertainment: Systematic eye examsScale: UnknownDenominator: RP2D⚠ Not comparable: grading scale not documented

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

0.6 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

33.3%

n=3 · innovaTV 201

0.9 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

33.3%

n=3 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

0.9 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

14.3%

n=7 · innovaTV 208

0.9 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

2.5%

n=79 · innovaTV 208

1.2 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

36.4%

n=11 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

1.2 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

33.3%

n=3 · innovaTV 201

1.2 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

25%

n=8 · innovaTV 208

1.2 mg/kg

IV Days 1,8,15 q28d then once every 3 weeks

20%

n=5 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

1.2 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

18.2%

n=11 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

1.2 mg/kg

IV weekly ×3 (Days 1, 8, 15 of 28-day cycle)

16.7%

n=6 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

1.8 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

33.3%

n=3 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (1q3w)

33.3%

n=3 · GEN701/NCT02552121 — solid-tumor safety (ovarian/cervical expansion)

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

33.3%

n=3 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

21%

n=101 · innovaTV 204

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

21%

n=250 · innovaTV 301

2 mg/kg

IV every 3 weeks (Q3W)

21%

n=101 · innovaTV 204

2 mg/kg

IV every 3 weeks (Q3W)

21%

n=250 · innovaTV 301

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

15.6%

n=250 · innovaTV 301

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

13.3%

n=15 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

10.9%

n=101 · innovaTV 204

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

7.1%

n=14 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

6.7%

n=15 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

6.7%

n=15 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

5.6%

n=36 · innovaTV 201

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

5.5%

n=55 · innovaTV 201

2 mg/kg

2.1%

2.0 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

n=101 · innovaTV 204

2.2 mg/kg

IV once every 3 weeks (Day 1 of 21-day cycle)

50%

n=6 · innovaTV 201

per parent study (continuation)

per parent study

20%

n=5 · NCT03245736 — continued-treatment rollover

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

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).