Brentuximab vedotin

FDA-approved

Adcetris; SGN-35

Target

CD30 · TNFRSF8

Sponsor

Seagen (now Pfizer)

Indication

CD30+ lymphoma

Target family

TNF receptor superfamily

RP2D dose

1.8 mg/kg (max 180 mg)

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

1 adverse-event term

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.56%

Limbus

Express.

0.9%

Conjunctiva

Express.

0.56%

Lens

Express.

Retina / RPE

Express.

1.16%

0 nTPM

Dominant tissue

Surface subtype

Unknown

Reversibility

Reversible

Reported ocular events

Uveitis (anterior/intermediate) — also blurred vision, dry eye, conjunctivitis as rare PTs-

Per-trial detail

Adverse events by trial

C25007 (R/R cHL or sALCL)Phase 41.8 mg/kg q3wn=60CTCAE 4.03PooledBto verify

CT.gov posted results NCT01990534 (AE module, all-cause deaths) NCT01990534

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

Infections17

Upper respiratory tract infection

8.3%

5/60

Bronchitis

3/60

Nasopharyngitis

3.3%

2/60

Oral herpes

3.3%

2/60

Subcutaneous abscess

3.3%

2/60

Breast cellulitis

1.7%

1/60

Conjunctivitis

1.7%

1/60

Coxsackie viral infection

1.7%

1/60

Dengue fever

1.7%

1/60

Device related infection

1.7%

1/60

Herpes zoster

1.7%

1/60

Hordeolum

1.7%

1/60

Influenza

1.7%

1/60

Klebsiella infection

1.7%

1/60

Pseudomonas infection

1.7%

1/60

Sinusitis

1.7%

1/60

Viral infection

1.7%

1/60

Dermatologic14

General13

Investigations11

Neurologic (other)9

GI6

Hematologic5

Metabolic5

Pulmonary5

Musculoskeletal4

Injury3

Psychiatric2

Vascular2

Overall/Summary1

Cardiac1

Ear1

Endocrine1

Ocular1

Diplopia

1.7%

1/60

Hepatic1

Renal1

Other1

Construct

Molecular anatomy

Antibody

IgG1

Chimeric

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

cAC10 (brentuximab)

Isotype

IgG1

Origin

Chimeric

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

Epitope / domain

Membrane-proximal CD30 extracellular epitope, residues aa 163-178

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

5.0 d

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Platform

Seagen 'vedotin' platform

Conjugation site

Interchain cysteines liberated by partial reduction of the 4 inter-chain disulfides

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

98%@10d/human-plasma

Stability note

acAb t½ 4–6 days; <2% free MMAE at 10 d in human plasma in vitro; 2–6%/day conjugate loss in cyno via retro-Michael (Alley 2008, Lyon 2014)

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

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

Potency IC50 (nM)

CAS no.

646502-53-6

Plasma protein binding (%)

68 %

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

ADCdb reports MMAE payload potency with IC50 as low as 1.9 pM in CD30+ Karpas-299 cells (range across cell lines up to ~3300 ng/mL). Mechanism: MMAE binds tubulin and disrupts microtubules, causing G2/M arrest and apoptosis after antigen-mediated internalization and Val-Cit linke

Dosing & regimen

Dosing

RP2D dose

1.8 mg/kg (max 180 mg)

Schedule

Q3W

Route

Fractionated

n at RP2D

885

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

ADA rate (%)

37 %

Pharmacology

Clinical pharmacokinetics

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

	Intact ADC	Total antibody	Free payload
Cmax	18.89 (27% CV)ug/mL+4	24.7 (26% CV)ug/mL+4	2.72 (272% CV)ng/mL+4
AUC	46.14 (62% CV)day*ug/mL+4	112.0 (27% CV)day*ug/mL+4	20.29 (212% CV)day*ng/mL+4
Tmax	near end of infusion(qualitative)+5	0.13 (0.08, 0.24)day+4	approximately 1-3 (after end of infusion)day+5
t½	approximately 4-6day+5	—	approximately 3-4day+5
CL	1.96 (105% CV)L/day+4	—	—
Vd	approximately 6-10L+5	—	—

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

5 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

1.5

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

Unknown

Grading scale

Mixed

Reversibility

Reversible

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

Cornea (central)

0.56 %

Cornea (limbal)

0.9 %

Conjunctiva

0.56 %

RPE

1.16 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Symptom-driven reportingScale: MixedDenominator: RP2D⚠ Not comparable: symptom-driven ascertainment + mixed grading scale

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

Identity & registry

Identifiers, registry & notes

ADC id

brentuximab-vedotin

Approval status

FDA-approved

Approval year

2011

UniProt

P28908

ADCdb ADC

DRG0JWBNH

ADCdb antibody

ANI0HIDZC

ADCdb target

TAR0QPCSQ

Primary source

ADCETRIS DailyMed label; imputed from >=10% reporting threshold

Aliases & development codes

Adcetris; SGN-35

Notes

5% imputed (label has no Eye disorders SOC at >=10% threshold)