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

Per-trial detail

Adverse events by trial

Moxetumomab + rituximab, relapsed HCL (NCT03805932) — combinationPhase 140 µg/kg moxetumomab + rituximab (dose-expansion) moxetumomab IV Days 1,3,5 + rituximab, every 28 daysn=15PooledB

ClinicalTrials.gov posted results — NCT03805932 (Other AE module) [1/15 patients] NCT03805932

94 adverse-event terms · 18 systems · expand a system below

Investigations16

Lymphocyte count decreased

100%

15/15

Aspartate aminotransferase increased

86.7%

13/15

Platelet count decreased

86.7%

13/15

White blood cell decreased

73.3%

11/15

Alanine aminotransferase increased

66.7%

10/15

Blood lactate dehydrogenase increased

46.7%

7/15

Neutrophil count decreased

26.7%

4/15

Haptoglobin decreased

20%

3/15

Blood bilirubin increased

20%

3/15

Creatinine increased

20%

3/15

CD4 lymphocytes decreased

13.3%

2/15

CPK increased

13.3%

2/15

GGT increased

6.7%

1/15

Lipase increased

6.7%

1/15

Lymphocyte count increased

6.7%

1/15

Serum amylase increased

6.7%

1/15

Metabolic12

GI9

General8

Renal7

Pulmonary7

Dermatologic6

Musculoskeletal5

Cardiac4

Neurologic (other)4

Vascular4

Ocular3

Eye disorders - Other, specify

6.7%

1/15

Eye pain

6.7%

1/15

Cataract

6.7%

1/15

Hematologic2

Injury2

Psychiatric2

Infections1

Neoplasms1

Other1

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

N/A

Effector silencing

N/A

FcγR binding

Abolished

C1q binding

Abolished

Target KD (nM)

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

0.058 d

Cleavage trigger

Furin protease + PDI reductive processing (intracellular)

Release control

Conditional

Hydrophilicity mask

N/A

Platform

Recombinant Pseudomonas-exotoxin immunotoxin

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

ADA rate (%)

75 %

Pharmacology

Clinical pharmacokinetics

By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews

	Intact ADC
Cmax	379 (SD 262; range 20-862)ng/mL+3
AUC	626 (SD 610; range 5-1960)ng·hour/mL (AUC0-last)+8
Tmax	0.567 (median; range 0.433-1.30)hour+2
t½	1.4 (SD 0.35; range 0.8-1.8)hour+3
CL	25 (SD 29.0)L/hour+5
Vd	6.5 (SD 2.4)L+1

FDA label §12.3 Drugs@FDA reviewhover a value for dose / population / source · “+N” marks additional reported values

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 v4.0

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: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D

Dose & schedule → ocular toxicity · ocular AE (any-grade) by cohort

0.04 mg/kg

Days 1, 3, and 5 of each 28-day cycle (IV over 30 min)

n=80 · Study 1053

5-50 µg/kg (escalation; schemas A/B/C)

IV QOD x3 (schema A) or x6 (schemas B/C) every 21-28 days

14.5%

n=55 · Phase 1 pediatric ALL/NHL

40 µg/kg

IV 30-min on Days 1, 3, 5 every 28 days

10%

n=30 · Phase 2 pediatric ALL

5-20 µg/kg (escalation; terminated)

IV QOD x3 (Days 1,3,5) every 28 days

9.1%

n=11 · Phase 1 chronic leukemia CLL/PLL

5-20 µg/kg (escalation; terminated)

IV QOD x3 (Days 1,3,5) every 28 days

9.1%

n=11 · Phase 1 chronic leukemia CLL/PLL

40 µg/kg

IV 30-min on Days 1, 3, 5 every 28 days (up to 6 cycles)

8.8%

n=80 · Study 1053

20-60 µg/kg (escalation)

IV QOD x3 (Days 1,3,5) every 28 days

8.7%

n=23 · Phase 1 B-NHL/CLL

40 µg/kg moxetumomab + rituximab (dose-expansion)

moxetumomab IV Days 1,3,5 + rituximab, every 28 days

6.7%

n=15 · Moxetumomab + rituximab, relapsed HCL

40 µg/kg

IV 30-min on Days 1, 3, 5 every 28 days

3.3%

n=30 · Phase 2 pediatric ALL

5-50 µg/kg (escalation; schemas A/B/C)

IV QOD x3 (schema A) or x6 (schemas B/C) every 21-28 days

1.8%

n=55 · Phase 1 pediatric ALL/NHL

Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

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.