ADC TOXICITY ATLAS
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Trastuzumab emtansine

FDA-approved
T-DM1; Kadcyla
Sponsor
Genentech/Roche
Indication
HER2+ breast cancer
Target family
Receptor tyrosine kinase
RP2D dose
3.6 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

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

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
46.2%
Limbus
AE
-
Express.
61.99%
Conjunctiva
AE
3.9%
Express.
61.13%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
5.48%
7.5 nTPM
Dominant tissue
Ocular surface
Surface subtype
Conjunctival (on-target)
Reversibility
Reversible
Reported ocular events
Lacrimation increased6%
n=740
Dry eye4.5%
n=740
Vision blurred3.9%
n=740
Conjunctivitis3.5%
n=740
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Non-cleavable
Non-cleavable
3.5
DAR
Payload
Lys-SMCC-DM1
Tubulin inhibitor
Linker structureC16H18N2O6
[H]C1=C([H])C(=O)N(C([H])([H])C2([H])C([H])([H])C([H])([H])C([H])(C(=O)ON3C(=O)C([H])([H])C([H])([H])C3=O)C([H])([H])C2([H])[H])C1=O
Payload structureC53H75ClN6O15S
CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)N(C)C(=O)CCSC5CC(=O)N(C5=O)CC6CCC(CC6)C(=O)NCCCCC(C(=O)O)N)C)C)OC)(NC(=O)O2)O
03
Antibody

Antibody & Fc engineering

Antibody
trastuzumab
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
SMCC
Class
Non-cleavable
Cleavage
Non-cleavable
Attachment
Lysine
Conjugation
Conventional Lys (SMCC)
Symmetry
Asymmetric
DAR (mean)
3.5
DAR homogeneity
Heterogeneous
Plasma t½
4.0 d
Cleavage trigger
Non-cleavable
Release control
Unconditional
Hydrophilicity mask
None
Formula
C16H18N2O6
Linker MW
334.328 Da
Linker TPSA
101.06 Ų
Linker xLogP
0.325
ADCdb linker
LIN0EBJON
In-vitro stability
-
Stability note
acAb t½ 3.94 d; SMCC is the highest intrinsic plasma stability among clinical linkers — non-cleavable thioether to charged Lys-MCC-DM1 catabolite (no bystander); deconjugation is not a significant pathway
05
Payload

Payload & physicochemistry

Payload profile
Payload
Lys-SMCC-DM1
Class
Maytansinoid
Mechanism
Tubulin inhibitor
Released catabolite
Lys-MCC-DM1 (lysine-Nε-MCC-DM1; = Lys-SMCC-DM1 in literature), the principal charged catabolite; MCC-DM1 and free DM1 also detected at low levels in plasma
Mechanistic subtype
Tubulin-maytansinoid
Stereochem / salt
-
Bystander
No
PAMPA rank
5
MW
1103.7 Da
XLogP3
-0.2
logD₇.₄
-0.5
TPSA
312 Ų
pKa
2.2 pKa
Charge pH 7.4
Zwitterion
H-bond donors
5
H-bond acceptors
17
IC50 (HCEC)
-
Formula
C53H75ClN6O15S
PubChem CID
74832310
ADCdb payload
PAY0JCIBW
Hydrophobicity · logD₇.₄
hydrophilic −2-0.5+4 lipophilic
Bioactivity note
ADCdb lists T-DM1 cellular IC50 values spanning ~0.04 nM (high HER2-expressing lines) to >500 nM (low/negative HER2 lines), HER2-expression dependent. No isolated free-payload (DM1) IC50 is given on the ADCdb ADC page; DM1 is a potent antimitotic maytansinoid that inhibits tubuli
06
Dosing & regimen

Dosing

RP2D dose
3.6 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
490
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
3.9 %
Dry eye
3.9 %
Blurred vision
4.5 %
Dominant tissue
Ocular surface
Surface subtype
Conjunctival (on-target)
Grading scale
CTCAE v3
Reversibility
Reversible
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
46.2 %
Cornea (limbal)
61.99 %
Conjunctiva
61.13 %
RPE
5.48 %
Retina (HPA)
7.5 nTPM
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: CTCAE v3Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
trastuzumab-emtansine
Approval status
FDA-approved
Approval year
2013
UniProt
P04626
ADCdb ADC
DRG0CYMEB
ADCdb antibody
ANI0FIZAK
ADCdb target
TAR0THKZD
Primary source
KADCYLA DailyMed label; EMILIA NEJM 2012
Aliases & development codes
T-DM1; Kadcyla
Notes
V3.1: Non-cleavable SMCC + charged Lys-MCC-DM1 catabolite → no bystander → low OAE despite high HER2 cornea expression. oae_any_pct=5.0 is DERIVED (sum of decomposed AEs); label gives individual Eye AEs only: conjunctivitis 3.9%, dry eye 3.9%, blurred vision 4.5%, lacrimation 3.3%. oae_g3plus_pct=0 derived (G3-4 not separately specified).