Denintuzumab mafodotin (ALL)

Discontinued

SGN-CD19A; ALL cohort

Target

CD19 · CD19

Sponsor

Seagen

Indication

CD19+ ALL

Target family

Immunoglobulin superfamily

RP2D dose

4-6 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

3 adverse-event terms

Ocular

Any-grade

56%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

56%

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

0.05%

0 nTPM

Off-target signature

56% corneal toxicity, yet the CD19 target is detected in only 0% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Keratopathy (microcystic)56%

n=71

Vision blurred35%

n=71

Keratopathy (microcystic) — Grade 3/4 corneal AE-

Per-trial detail

Adverse events by trial

SGN19A-001 (NCT01786096), adult subsetPhase 10.3-6 mg/kg (both schedules pooled) Weekly (D1,8 q21d) or q3wkn=71PooledDto verify

Fathi, Blood 2015;126(23):1328 (ASH 2015 abstr #1328) Blood 2015;126(23):1328 / NCT01786096

8 adverse-event terms · 1 system · expand a system below

Other8

Pyrexia

54%

38/71

Nausea

52%

37/71

Fatigue

51%

36/71

Headache

44%

31/71

Chills

38%

27/71

Vomiting

37%

26/71

Blurred vision

35%

25/71

Anemia

34%

24/71

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Non-cleavable

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

Antibody

Antibody & Fc engineering

Antibody

SGN-CD19 (denintuzumab)

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Dev code

BU12

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)

DAR homogeneity

Heterogeneous

Plasma t½

14.0 d

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

None

Conjugation site

Reduced interchain disulfide cysteines

Formula

C10H13NO4

Linker MW

211.217 Da

Linker TPSA

74.68 Å²

Linker xLogP

0.5564

ADCdb linker

LIN0TAFAV

In-vitro stability

Stability note

Same ADC as NHL cohort (different population, ALL); inherited per-ADC PK from Fathi 2015; Blanc 2015 ASH abstract for ALL cohort does not separately tabulate t½

Payload

Payload & physicochemistry

Payload profile

Payload

Cys-mcMMAF

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

Cys-mcMMAF

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

PAMPA rank

1046.3 Da

XLogP3

1.4

logD₇.₄

-1

TPSA

301 Å²

pKa

3.5 pKa

Charge pH 7.4

-1

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C52H83N7O13S

PubChem CID

86278355

ADCdb payload

PAY0QLDVX

CAS no.

1399672-02-6

Permeability (Papp)

Low

Hydrophobicity · logD₇.₄

hydrophilic −2-1+4 lipophilic

Bioactivity note

ADCdb payload page (PAY0QLDVX, MMAF) lists free-MMAF cytotoxicity IC50 values: SK-BR-3 5.3 nM, Hep-G2 7 nM, BT474-M1 8.8 nM, HT-29 10 nM, H3396 105 nM, HL-60 137 nM, HCT 116 2880 nM. No ADC-level (SGN-CD19A) binding/efficacy IC50 reported on the ADCdb ADC page; ADC was in Phase 1

Dosing & regimen

Dosing

RP2D dose

4-6 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

56 %

OAE grade 3+

OAE data status

reported

Severity (weighted)

Keratopathy

56 %

Conjunctival

Dry eye

Blurred vision

35 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4.03

Reversibility

Reversible

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

Cornea (central)

0 %

Cornea (limbal)

0 %

Conjunctiva

0 %

RPE

0.05 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: UnknownDenominator: RP2D⚠ Not comparable: grading scale not documented

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

Identity & registry

Identifiers, registry & notes

ADC id

denintuzumab-mafodotin-all

Approval status

Discontinued

Approval year

UniProt

P15391

ADCdb ADC

DRG0OVAOS

ADCdb antibody

ANI0VYXVW

ADCdb target

TAR0EBTXG

Primary source

Blanc Blood 2015 ASH abstract (126:1328)

Aliases & development codes

SGN-CD19A; ALL cohort

Notes

Same ADC as NHL cohort; different population. V3.1: 56% keratopathy + 35% blurred verified. n=71 is total adults; includes weekly 0.3-3 mg/kg + Q3W 4-6 mg/kg cohorts.