ADC TOXICITY ATLAS
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Depatuxizumab mafodotin

Discontinued
ABT-414; depatux-m
Sponsor
AbbVie
Indication
EGFR-amplified GBM
Target family
Receptor tyrosine kinase
RP2D dose
1.25 mg/kg
Q2WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
94%
G3+
60%
RP2D
sagittal schematic · Mixed
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
94%
Express.
89.35%
Limbus
AE
-
Express.
97.58%
Conjunctiva
AE
-
Express.
93.02%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
83.36%
9.4 nTPM
Off-target signature

94% corneal toxicity, yet the EGFR target is detected in only 89.35% of central cornea - toxicity is not explained by target expression.

Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Reversibility
Mixed
Reported ocular events
Corneal epitheliopathy (composite)94%
G3+ 60.4%n=323
Corneal epitheliopathy (eye disorders, composite)71.4%
G3+ 23.8%n=84
Vision blurred65%
G3+ 5%n=66
Keratopathy62%
Dry eye29%
G3+ 3%n=66
Keratitis27%
G3+ 17%n=66
Photophobia27%
n=66
Eye pain26%
n=66
Punctate keratitis7.9%
Corneal epithelial microcysts6.4%
Lacrimation increased5.8%
Cataract4.8%
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Non-cleavable
Non-cleavable
4
DAR
Payload
Cys-mcMMAF
Tubulin inhibitor
Linker structureC10H13NO4
O=C(O)CCCCCN1C(=O)C=CC1=O
Payload structureC52H83N7O13S
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN3C(=O)CC(C3=O)SC[C@@H](C(=O)O)N
03
Antibody

Antibody & Fc engineering

Antibody
ABT-806 (depatuxizumab)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
mc (non-cleavable)
Class
Non-cleavable
Cleavage
Non-cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
Symmetry
Symmetric
DAR (mean)
4
DAR homogeneity
Heterogeneous
Plasma t½
10.0 d
Cleavage trigger
Non-cleavable
Release control
Unconditional
Hydrophilicity mask
None
Formula
C10H13NO4
Linker MW
211.217 Da
Linker TPSA
74.68 Ų
Linker xLogP
0.5564
ADCdb linker
LIN0TAFAV
In-vitro stability
-
Stability note
Harmonic mean terminal t½: depatux-m (intact ADC) ~10 d; total depatux ~12 d; cys-mafodotin (released payload) ~4 d (Goss Cancer 2018 advanced solid tumor Ph1). Linear PK; no target-mediated disposition
05
Payload

Payload & physicochemistry

Payload profile
Payload
Cys-mcMMAF
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
Cys-mcMMAF (Cys-mafodotin)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
No
PAMPA rank
6
MW
1046.3 Da
XLogP3
1.4
logD₇.₄
-1
TPSA
301 Ų
pKa
3.5 pKa
Charge pH 7.4
-1
H-bond donors
5
H-bond acceptors
15
IC50 (HCEC)
-
Formula
C52H83N7O13S
PubChem CID
86278355
ADCdb payload
PAY0QLDVX
Hydrophobicity · logD₇.₄
hydrophilic −2-1+4 lipophilic
Bioactivity note
ADCdb (DRG0PXQWR) reports IC50 range 10.00-35.00 ug/mL across mesothelioma cell lines and tumor growth inhibition of approximately 87.5% in the MSTO-211H xenograft model. The free payload MMAF/Cys-mcMMAF is a potent tubulin polymerization inhibitor (anti-microtubule auristatin).
06
Dosing & regimen

Dosing

RP2D dose
1.25 mg/kg
Schedule
Q2W
Route
IV
Fractionated
No
n at RP2D
323
Dose basis
TBW
Trial phase
Phase 3
Dose-OAE available
Yes
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
94 %
OAE grade 3+
60 %
OAE data status
reported
Severity (weighted)
70.2
Keratopathy
94 %
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Grading scale
CTCAE v4
Reversibility
Mixed
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
89.35 %
Cornea (limbal)
97.58 %
Conjunctiva
93.02 %
RPE
83.36 %
Retina (HPA)
9.4 nTPM
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
depatuxizumab-mafodotin
Approval status
Discontinued
Approval year
-
UniProt
P00533
ADCdb ADC
DRG0PXQWR
ADCdb antibody
ANI0TJUOM
ADCdb target
TAR0UYFIF
Primary source
Lassman INTELLANCE-1 Neuro-Oncol 2023; PMC9925712
Aliases & development codes
ABT-414; depatux-m
Notes
V3.1 MAJOR CORRECTION: G3+ OAE 27→60% per Lassman Neuro-Oncol 2023 INTELLANCE-1 direct quote ('Grade 3 CE 55%, grade 4 perforation/blindness 5%'). Prior 27% misattributed. Severity ratio now 0.638 (was 0.287).