ADC TOXICITY ATLAS
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Brentuximab vedotin

FDA-approved
Adcetris; SGN-35
Sponsor
Seagen (now Pfizer)
Indication
CD30+ lymphoma
Target family
TNF receptor superfamily
RP2D dose
1.8 mg/kg (max 180 mg)
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
1 adverse-event term

Ocular

Any-grade
5%
G3+
0%
RP2D
sagittal schematic · Unknown
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
0.56%
Limbus
AE
-
Express.
0.9%
Conjunctiva
AE
-
Express.
0.56%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
1.16%
0 nTPM
Dominant tissue
-
Surface subtype
Unknown
Reversibility
Unknown
Reported ocular events
Uveitis (anterior/intermediate) — also blurred vision, dry eye, conjunctivitis as rare PTs-
02
Construct

Molecular anatomy

Antibody
IgG1
Chimeric
Linker
Cleavable
Cleavable
4
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
03
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
04
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)
4
DAR homogeneity
Heterogeneous
Plasma t½
5.0 d
Cleavage trigger
Cathepsin B (Val-Cit)
Release control
Conditional
Hydrophilicity mask
None
Formula
C28H40N6O7
Linker MW
572.663 Da
Linker TPSA
200.03 Ų
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)
05
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
1
MW
718 Da
XLogP3
4.1
logD₇.₄
2.7
TPSA
150 Ų
pKa
9.1 pKa
Charge pH 7.4
+1
H-bond donors
4
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C39H67N5O7
PubChem CID
11542188
ADCdb payload
PAY0FSXOW
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
06
Dosing & regimen

Dosing

RP2D dose
1.8 mg/kg (max 180 mg)
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
885
Dose basis
TBW
Trial phase
Approved
Dose-OAE available
No
Tox summary basis
RP2D
07
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
Unknown
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⚠ OAE rate not directly comparable across trials
08
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)