ADC TOXICITY ATLAS
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Gemtuzumab ozogamicin

FDA-approved
Mylotarg; CMA-676
Sponsor
Wyeth/Pfizer
Indication
CD33+ AML
Target family
Siglec
RP2D dose
3 mg/m² (max 4.5 mg)
D1+D4+D7 inductionRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

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

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
0.07%
Limbus
AE
-
Express.
0.03%
Conjunctiva
AE
-
Express.
0.06%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
0.46%
0.2 nTPM
Dominant tissue
-
Surface subtype
None
Reversibility
Unknown
Reported ocular events
No granular adverse-event rows recorded for this system.
Per-trial detail

Adverse events by trial

Combination Chemotherapy With or Without G (NCT00372593)Phase 3n=511CTCAE NRB
ClinicalTrials.gov posted results, NCT00372593 NCT00372593
291 adverse-event terms · 22 systems · expand a system below
GI48
Mucositis oral
18.4%G3+ 0%
94/511
Nausea
12.1%
62/511
Diarrhea
11.4%
58/511
Abdominal pain
8.6%
44/511
Vomiting
8.6%
44/511
Oral pain
6.8%
35/511
Typhlitis
6.1%
31/511
Ascites
3.7%G3+ 0%
19/511
Esophagitis
2.3%
12/511
Colitis
1.8%
9/511
Ileus
1.8%
9/511
Rectal pain
1.8%
9/511
Gastrointestinal disorders - Other
1.6%
8/511
Anal pain
1.4%
7/511
Lower gastrointestinal hemorrhage
1%
5/511
Abdominal distension
0.8%
4/511
Gastritis
0.6%G3+ 0%
3/511
Anal mucositis
0.6%
3/511
Dysphagia
0.6%
3/511
Pancreatitis
0.6%
3/511
Upper gastrointestinal hemorrhage
0.6%
3/511
Dyspepsia
0.4%
2/511
Enterocolitis
0.4%
2/511
Esophageal pain
0.4%
2/511
Gingival pain
0.4%
2/511
Malabsorption
0.2%
1/511
Cheilitis
0.2%
1/511
Dental caries
0.2%
1/511
Esophageal hemorrhage
0.2%
1/511
Gastrointestinal pain
0.2%
1/511
Hemorrhoids
0.2%
1/511
Oral hemorrhage
0.2%
1/511
Rectal mucositis
0.2%
1/511
Small intestinal obstruction
0.2%
1/511
Toothache
0.2%
1/511
Anal ulcer
0%
0/511
Colonic fistula
0%
0/511
Colonic hemorrhage
0%
0/511
Constipation
0%
0/511
Duodenal hemorrhage
0%
0/511
Gastric hemorrhage
0%
0/511
Intra-abdominal hemorrhage
0%
0/511
Lip pain
0%
0/511
Proctitis
0%
0/511
Rectal fistula
0%
0/511
Rectal hemorrhage
0%
0/511
Small intestinal mucositis
0%
0/511
Stomach pain
0%
0/511
Infections36
Pulmonary24
Investigations20
Metabolic20
Neurologic (other)17
Cardiac15
Musculoskeletal15
General14
Dermatologic11
Injury9
Renal9
Hepatic8
Psychiatric8
Ocular7
Eye pain
1%
5/511
Photophobia
0.8%
4/511
Blurred vision
0.4%
2/511
Conjunctivitis
0.2%
1/511
Eye disorders - Other
0.2%
1/511
Uveitis
0.2%
1/511
Vitreous hemorrhage
0.2%
1/511
Other7
Vascular7
Ear5
Hematologic4
Immune4
Endocrine2
Neoplasms1
02
Construct

Molecular anatomy

Antibody
IgG4
Humanized
Linker
Cleavable
Cleavable
2.5
DAR
Payload
Calicheamicin gamma1
DNA strand break
Linker structureC12H15NO3
CC(=O)c1ccc(OCCCC(N)=O)cc1
Payload structureC55H74IN3O21S4
CCN[C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\\C#C[C@@]\\4(CC(=O)C(=C3/C4=C\\CSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O
03
Antibody

Antibody & Fc engineering

Antibody
hP67.6
Isotype
IgG4
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Reduced
Epitope / domain
CD33 IgV
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
AcBut hydrazone + disulfide
Class
Cleavable
Cleavage
Cleavable
Attachment
Lysine
Conjugation
Conventional Lys (NHS)
Symmetry
Asymmetric
DAR (mean)
2.5
DAR homogeneity
Heterogeneous
Plasma t½
2.6 d
Cleavage trigger
pH/acid (hydrazone) + GSH/reductive (disulfide)
Release control
Conditional
Hydrophilicity mask
None
Cell line
NS0
Formula
C12H15NO3
Linker MW
221.256 Da
Linker TPSA
69.39 Ų
Linker xLogP
1.5335
ADCdb linker
LIN0KWKDL
In-vitro stability
-
Stability note
Terminal t½ ~62 h after dose 1, ~90 h after dose 2 (9 mg/m² regimen); acid-labile hydrazone + disulfide intentionally plasma-labile, implicated in hepatotoxicity / VOD-SOS
05
Payload

Payload & physicochemistry

Payload profile
Payload
Calicheamicin gamma1
Class
Calicheamicin
Mechanism
DNA strand break
Released catabolite
N-acetyl-γ-calicheamicin (active calicheamicin derivative), released from the conjugated N-acetyl-γ-calicheamicin dimethylhydrazide (N-Ac-γ-cal-DMH) by nonenzymatic reduction of the disulfide bond
Mechanistic subtype
DNA-strand-break
Stereochem / salt
-
Bystander
Partial
PAMPA rank
6
MW
1368.4 Da
XLogP3
2
logD₇.₄
2
TPSA
410 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
8
H-bond acceptors
27
IC50 (HCEC)
-
Formula
C55H74IN3O21S4
PubChem CID
10953353
ADCdb payload
PAY0RZSDY
Plasma protein binding (%)
97 %
Hydrophobicity · logD₇.₄
hydrophilic −2+2+4 lipophilic
Bioactivity note
ADCdb (DRG0JOHND) reports payload/ADC potency against CD33+ cells with most potent IC50 ~20 pM (ML-2) and ~30 pM (MOLM-13, EoL-1); clinical objective response rate ~85% in CD33+ AML. Calicheamicin warhead induces sequence-selective double-strand DNA breaks (ADCdb lists the mechan
06
Dosing & regimen

Dosing

RP2D dose
3 mg/m² (max 4.5 mg)
Schedule
D1+D4+D7 induction
Route
IV
Fractionated
Yes
n at RP2D
131
Dose basis
BSA
Trial phase
Approved
Dose-OAE available
No
Tox summary basis
RP2D
07
Pharmacology

Clinical pharmacokinetics

By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews
Intact ADCTotal antibodyFree payload
Cmax—
3.0mg/L+1
—
Tmax
2h
2h
2h
t½
~41h+1
62h+3
—
CL—
0.35L/h+1
—
Vd—
21.4L+2
—
FDA label §12.3 Drugs@FDA reviewhover a value for dose / population / source · “+N” marks additional reported values
08
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
0 %
OAE grade 3+
0 %
OAE data status
documented-absent
Severity (weighted)
0
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
-
Surface subtype
None
Grading scale
CTCAE v3.0
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
0.07 %
Cornea (limbal)
0.03 %
Conjunctiva
0.06 %
RPE
0.46 %
Retina (HPA)
0.2 nTPM
Cross-trial comparability
Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ Not comparable: symptom-driven ascertainment + grading scale not documented
Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification
09
Identity & registry

Identifiers, registry & notes

ADC id
gemtuzumab-ozogamicin
Approval status
FDA-approved
Approval year
2000
UniProt
P20138
ADCdb ADC
DRG0JOHND
ADCdb antibody
ANI0AZCDK
ADCdb target
TAR0OVWVF
Primary source
FDA Mylotarg label (DailyMed)
Aliases & development codes
Mylotarg; CMA-676
Notes
Hematologic target; both routes to cornea closed (no expression + hydrophilic payload). V3.1: n=131 (ALFA-0701 pivotal, basis for 2017 reapproval); prior 242 not in label.