Moxetumomab pasudotox

FDA-approved

Lumoxiti; CAT-8015

Target

CD22 · CD22

Sponsor

AstraZeneca (AZ/MedImmune)

Indication

Hairy cell leukemia (CD22)

Target family

Siglec

RP2D dose

0.04 mg/kg

D1+D3+D5 Q4WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

8 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.5%

Limbus

Express.

1.1%

Conjunctiva

1.3%

Express.

1.64%

Lens

Express.

Retina / RPE

Express.

1.16%

0 nTPM

Dominant tissue

Mixed

Surface subtype

Mixed

Reversibility

Reversible

Reported ocular events

Vision blurred9%

n=80

Dry eye8%

n=80

Cataract5%

n=80

Eye pain / ocular discomfort4%

n=80

Eye swelling / periorbital oedema4%

n=80

Conjunctivitis1.3%

n=80

Conjunctival haemorrhage1.3%

n=80

Eye discharge1.3%

n=80

Construct

Molecular anatomy

Antibody

Other

Murine

Linker

Cleavable

Undisclosed (per ADCdb); not applicable as a stoichiometric DAR -- this is a 1:1 genetic fusion of one Fv to one PE38 toxin

DAR

Payload

PE38 (Pseudomonas exotoxin)

ADP-ribosyl. eEF2 (protein)

Linker structure

structure not applicable

Payload structure

structure not applicable

Antibody

Antibody & Fc engineering

Antibody

dsFv of RFB4

Isotype

Other

Origin

Murine

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Abolished

C1q binding

Abolished

Linker & conjugation

Linker chemistry

Linker profile

Linker

Recombinant dsFv-PE38 fusion

Class

Cleavable

Cleavage

Cleavable

Attachment

Genetic fusion

Conjugation

Not applicable (recombinant fusion)

Symmetry

N/A

DAR (mean)

Undisclosed (per ADCdb); not applicable as a stoichiometric DAR -- this is a 1:1 genetic fusion of one Fv to one PE38 toxin

DAR homogeneity

N/A

Plasma t½

0.08 d

Cleavage trigger

Furin protease + PDI reductive processing (intracellular)

Release control

Conditional

Hydrophilicity mask

N/A

Formula

Linker MW

Linker TPSA

Linker xLogP

ADCdb linker

In-vitro stability

Stability note

Recombinant immunotoxin (~63 kDa); short half-life 1–2 h after first dose due to renal clearance and immunogenicity; range 1–9 h on repeat dosing in cyno; not a chemical-linker ADC

Payload

Payload & physicochemistry

Payload profile

Payload

PE38 (Pseudomonas exotoxin)

Class

Other

Mechanism

ADP-ribosyl. eEF2 (protein)

Released catabolite

Unknown

Mechanistic subtype

Other

Stereochem / salt

Bystander

PAMPA rank

38000 Da

XLogP3

logD₇.₄

TPSA

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

PubChem CID

ADCdb payload

PAY0WCEKW

Bioactivity note

No molecular IC50/potency disclosed in ADCdb or PubChem. ADCdb reports clinical efficacy only: objective response rates ranging ~13% to 100% across trials/doses/indications (relapsed/refractory hairy cell leukemia and ALL). Mechanism: PE38 catalyzes ADP-ribosylation of eukaryotic

Dosing & regimen

Dosing

RP2D dose

0.04 mg/kg

Schedule

D1+D3+D5 Q4W

Route

Fractionated

Yes

n at RP2D

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

9 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

Keratopathy

Conjunctival

1.3 %

Dry eye

8 %

Blurred vision

9 %

Dominant tissue

Mixed

Surface subtype

Mixed

Grading scale

CTCAE v4

Reversibility

Reversible

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

Cornea (central)

0.5 %

Cornea (limbal)

1.1 %

Conjunctiva

1.64 %

RPE

1.16 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

moxetumomab-pasudotox

Approval status

FDA-approved

Approval year

2018

UniProt

P20273

ADCdb ADC

DRG0VJOET

ADCdb antibody

ANI0NZMLO

ADCdb target

TAR0XTCGM

Primary source

FDA Lumoxiti label; Kreitman NEJM 2018

Aliases & development codes

Lumoxiti; CAT-8015

Notes

Recombinant dsFv-PE38 immunotoxin. V3.1 correction: origin is murine (label explicit); n=80 pivotal (prev 145 not in label). OAE 0% was WRONG — label reports blurred vision 9%, dry eye 8%, conjunctivitis 1.3%, conjunctival hemorrhage 1.3%, cataracts 5%. Aggregate any-grade not tabulated. Capillary leak dominant toxicity.