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

50 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%

n=250

Dry eye29%

G3+ 0%n=101

Corneal adverse reactions21%

G3+ 3%n=101

Keratopathy17%

n=33

Periorbital adverse reactions16%

G3+ 0%n=101

Keratitis15.6%

non-seriousn=250

Vision blurred10.64%

non-seriousn=94

Lacrimation increased7.45%

non-seriousn=94

Vital dye staining cornea present6.06%

non-seriousn=33

Eye discharge5.32%

non-seriousn=94

Blepharitis5%

n=94

Punctate keratitis4.26%

non-seriousn=94

Ocular hyperaemia3.96%

non-seriousn=101

Entropion3.19%

non-seriousn=94

Episcleritis3.03%

non-seriousn=33

Meibomianitis2.97%

non-seriousn=101

Eye irritation2.56%

non-seriousn=195

Conjunctival haemorrhage2.13%

non-seriousn=94

Eye pain2.13%

non-seriousn=94

Cataract nuclear2.13%

non-seriousn=94

Conjunctivitis viral2.13%

non-seriousn=94

Corneal abrasion2.13%

non-seriousn=94

Ulcerative keratitis2.1%

n=101

Conjunctival scar2.05%

non-seriousn=195

Noninfective conjunctivitis2.05%

non-seriousn=195

Cataract1.98%

non-seriousn=101

Conjunctival hyperaemia1.98%

non-seriousn=101

Trichiasis1.98%

non-seriousn=101

Conjunctival ulcer1.4%

n=94

Ulcerative keratitis, severe1.2%

G3+

Conjunctivitis allergic1.06%

non-seriousn=94

Dacryostenosis acquired1.06%

non-seriousn=94

Ectropion1.06%

non-seriousn=94

Conjunctival disorder1.03%

non-seriousn=195

Eye pruritus1.03%

non-seriousn=195

Foreign body sensation in eyes1.03%

non-seriousn=195

Corneal erosion0.9%

n=101

Chemical burns of eye0.51%

non-seriousn=195

Chorioretinopathy0.51%

non-seriousn=195

Conjunctival staining0.51%

non-seriousn=195

Conjunctivitis bacterial0.51%

non-seriousn=195

Eye infection0.51%

non-seriousn=195

Eye inflammation0.51%

non-seriousn=195

Eyelid contusion0.51%

non-seriousn=195

Open angle glaucoma0.51%

non-seriousn=195

Periorbital oedema0.51%

non-seriousn=195

Retinal vein occlusion0.51%

non-seriousn=195

Conjunctival erosion0.5%

Symblepharon0.5%

n=94

Per-trial detail

Adverse events by trial

Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid TumorsPHASE1|PHASE2real-worldn=195CTCAE NR (ClinicalTrials.govPooledC

ClinicalTrials.gov NCT02001623 posted results, adverse events module (non-serious; 35/195 pooled across arms)

315 adverse-event terms · 21 systems · expand a system below

GI35

Constipation

39.39%non-serious

77/195

Diarrhoea

36.36%non-serious

71/195

Nausea

36.36%non-serious

71/195

Abdominal pain

33.33%non-serious

65/195

Vomiting

21.21%non-serious

41/195

Stomatitis

6.67%non-serious

13/195

Abdominal discomfort

6.06%non-serious

12/195

Abdominal pain upper

6.06%non-serious

12/195

Dry mouth

6.06%non-serious

12/195

Dyspepsia

6.06%non-serious

12/195

Abdominal pain lower

3.03%non-serious

6/195

Haematochezia

3.03%non-serious

6/195

Melaena

3.03%non-serious

6/195

Mouth ulceration

3.03%non-serious

6/195

Rectal haemorrhage

3.03%non-serious

6/195

Lip ulceration

3.03%non-serious

6/195

Rectal discharge

3.03%non-serious

6/195

Tongue blistering

3.03%non-serious

6/195

Colitis

2.05%non-serious

4/195

Dysphagia

2.05%non-serious

4/195

Ascites

1.54%non-serious

3/195

Gastrooesophageal reflux disease

1.54%non-serious

3/195

Haemorrhoids

1.54%non-serious

3/195

Abdominal distension

1.03%non-serious

2/195

Flatulence

1.03%non-serious

2/195

Gastritis

1.03%non-serious

2/195

Gingival bleeding

1.03%non-serious

2/195

Tongue ulceration

1.03%non-serious

2/195

Cheilitis

0.51%non-serious

1/195

Haematemesis

0.51%non-serious

1/195

Oesophageal mucosal hyperplasia

0.51%non-serious

1/195

Oesophagitis

0.51%non-serious

1/195

Oral pain

0.51%non-serious

1/195

Proctalgia

0.51%non-serious

1/195

Salivary hypersecretion

0.51%non-serious

1/195

Ocular35

Conjunctivitis

51.52%non-serious

100/195

Dry eye

18.18%non-serious

35/195

Blepharitis

9.09%non-serious

18/195

Eye pain

9.09%non-serious

18/195

Keratitis

9.09%non-serious

18/195

Vision blurred

7.18%non-serious

14/195

Meibomianitis

6.06%non-serious

12/195

Punctate keratitis

6.06%non-serious

12/195

Symblepharon

6.06%non-serious

12/195

Vital dye staining cornea present

6.06%non-serious

12/195

Conjunctival ulcer

4.62%non-serious

9/195

Lacrimation increased

3.03%non-serious

6/195

Ocular hyperaemia

3.03%non-serious

6/195

Ulcerative keratitis

3.03%non-serious

6/195

Episcleritis

3.03%non-serious

6/195

Keratopathy

3.03%non-serious

6/195

Conjunctival haemorrhage

2.56%non-serious

5/195

Eye irritation

2.56%non-serious

5/195

Conjunctival scar

2.05%non-serious

4/195

Noninfective conjunctivitis

2.05%non-serious

4/195

Cataract

1.54%non-serious

3/195

Conjunctival hyperaemia

1.54%non-serious

3/195

Conjunctival disorder

1.03%non-serious

2/195

Eye pruritus

1.03%non-serious

2/195

Foreign body sensation in eyes

1.03%non-serious

2/195

Chemical burns of eye

0.51%non-serious

1/195

Chorioretinopathy

0.51%non-serious

1/195

Conjunctival staining

0.51%non-serious

1/195

Conjunctivitis bacterial

0.51%non-serious

1/195

Eye infection

0.51%non-serious

1/195

Eye inflammation

0.51%non-serious

1/195

Eyelid contusion

0.51%non-serious

1/195

Open angle glaucoma

0.51%non-serious

1/195

Periorbital oedema

0.51%non-serious

1/195

Retinal vein occlusion

0.51%non-serious

1/195

Investigations29

Pulmonary29

Infections26

Neurologic (other)24

Dermatologic24

General17

Metabolic16

Musculoskeletal16

Renal12

Psychiatric9

Vascular8

Injury6

Other6

Hematologic5

Cardiac5

Ear5

Immune3

Neoplasms3

Hepatic2

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^inferred

Glycoengineering

Standard^inferred

Effector silencing

None^inferred

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^inferred

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)^ambiguous

Grading scale

CTCAE v5.0^locator?

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 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%

2.2 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

—

15.6%

n=250 · innovaTV 301

—

9.09%

n=195 · Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors

—

2.13%

n=94 · A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian

—

1.98%

n=101 · A Trial of Tisotumab Vedotin in Cervical Cancer

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).