Vadastuximab talirine

Discontinued

SGN-CD33A; anti-CD33 PBD

Target

CD33 · CD33

Sponsor

Seagen

Indication

CD33+ AML

Target family

Siglec

RP2D dose

40 mcg/kg

Q3W (or D1+D4 split)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

11 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Partial

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.07%

Limbus

Express.

0.03%

Conjunctiva

Express.

0.06%

Lens

Express.

Retina / RPE

Express.

0.46%

0.2 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Partial

Reported ocular events

Vision blurred10.53%

non-seriousn=19

Conjunctival haemorrhage7.14%

non-seriousn=14

Dry eye7.14%

non-seriousn=14

Eye discharge7.14%

non-seriousn=14

Eye pain7.14%

non-seriousn=14

Eye pruritus7.14%

non-seriousn=14

Graft versus host disease in eye7.14%

non-seriousn=14

Cataract5.26%

non-seriousn=19

Corneal opacity5.26%

non-seriousn=19

Intraocular pressure increased5.26%

non-seriousn=19

Photophobia5.26%

non-seriousn=19

Per-trial detail

Adverse events by trial

CASCADE: 33A + azacitidine/decitabine, frontline older AML (NCT02785900)Phase 310 mcg/kg IV q4wn=111CTCAE NRPooledBto verify

ClinicalTrials.gov posted results, NCT02785900 NCT02785900

220 adverse-event terms · 20 systems · expand a system below

Infections54

Sepsis

12.6%G3+

14/111

Pneumonia

9%other cohortG3+ 19.8%

10/111

Cellulitis

9%G3+ 5.4%

10/111

Lung infection

8.1%G3+

9/111

Septic shock

5.4%G3+

6/111

Oral candidiasis

5.4%

6/111

Urinary tract infection

3.6%G3+ 1.8%

4/111

Klebsiella sepsis

2.7%G3+

3/111

Diverticulitis

1.8%G3+

2/111

Bacteraemia

1.8%G3+

2/111

Staphylococcal infection

1.8%G3+

2/111

Device related infection

1.8%G3+

2/111

Infection

1.8%G3+

2/111

Pseudomonal sepsis

1.8%G3+

2/111

Streptococcal sepsis

1.8%G3+

2/111

Oral herpes

1.8%

2/111

Upper respiratory tract infection

0.9%G3+

1/111

Bronchitis

0.9%G3+

1/111

Abdominal infection

0.9%G3+

1/111

Influenza

0.9%G3+

1/111

Lower respiratory tract infection

0.9%G3+

1/111

Neutropenic sepsis

0.9%G3+

1/111

Anal abscess

0.9%G3+

1/111

Catheter site cellulitis

0.9%G3+

1/111

Cellulitis staphylococcal

0.9%G3+

1/111

Diarrhoea infectious

0.9%G3+

1/111

Enterobacter bacteraemia

0.9%G3+

1/111

Enterococcal bacteraemia

0.9%G3+

1/111

Enterococcal sepsis

0.9%G3+

1/111

Parotitis

0.9%G3+

1/111

Pharyngitis

0.9%G3+

1/111

Pneumonia respiratory syncytial viral

0.9%G3+

1/111

Postoperative wound infection

0.9%G3+

1/111

Sialoadenitis

0.9%G3+

1/111

Sinusitis

0.9%G3+

1/111

Skin infection

0.9%G3+

1/111

Soft tissue infection

0.9%G3+

1/111

Urinary tract infection bacterial

0%G3+

0/111

Acinetobacter bacteraemia

0%G3+

0/111

Bronchopulmonary aspergillosis

0%G3+

0/111

Clostridium difficile colitis

0%G3+

0/111

Clostridium difficile infection

0%G3+

0/111

Enterococcal infection

0%G3+

0/111

Escherichia sepsis

0%G3+

0/111

Necrotising fasciitis

0%G3+

0/111

Pilonidal cyst

0%G3+

0/111

Pneumonia fungal

0%G3+

0/111

Pneumonia influenzal

0%G3+

0/111

Pseudomonal bacteraemia

0%G3+

0/111

Pseudomonas infection

0%G3+

0/111

Staphylococcal sepsis

0%G3+

0/111

Subcutaneous abscess

0%G3+

0/111

Tonsillitis

0%G3+

0/111

Tooth abscess

0%G3+

0/111

GI24

Cardiac19

General15

Metabolic14

Pulmonary14

Investigations13

Neurologic (other)10

Hematologic9

Vascular8

Injury7

Musculoskeletal6

Hepatic5

Psychiatric5

Renal5

Dermatologic5

Neoplasms4

Overall/Summary1

Ear1

Other1

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

SGD-1882

DNA cross-linker

Linker structureC18H27N3O6

[H]OC(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(=O)C([H])=C([H])C1=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H]

Payload structureC42H39N5O7

COC1=CC=C(C=C1)C2=CN3[C@@H](C2)C=NC4=CC(=C(C=C4C3=O)OC)OCCCOC5=C(C=C6C(=C5)N=C[C@@H]7CC(=CN7C6=O)C8=CC=C(C=C8)N)OC

Antibody

Antibody & Fc engineering

Antibody

anti-CD33 (vadastuximab)

Isotype

IgG1^unver.

Origin

Humanized^unver.

Fc modifications

EC-mAb engineered Cys^unver.

Glycoengineering

Standard^inferred

Effector silencing

None^inferred

FcγR binding

Retained

C1q binding

Unknown^inferred

Dev code

h2H12 / h2H12ec^{wrong paper}

Linker & conjugation

Linker chemistry

Linker profile

Linker

VA dipeptide + engineered Cys (EC-mAb)^unver.

Class

Cleavable^unver.

Cleavage

Cleavable^unver.

Attachment

Site-specific (engineered Cys)^unver.

Conjugation

Site-specific engineered Cys (EC-mAb)^unver.

Symmetry

Site-specific (paired)^unver.

DAR (mean)

DAR homogeneity

Homogeneous^unver.

Plasma t½

7.0 d

Cleavage trigger

Cathepsin B (Val-Ala)

Release control

Conditional

Hydrophilicity mask

None^inferred

Platform

EC-mAb^unver.

Conjugation site

S239C^unver.

Formula

C18H27N3O6

Linker MW

381.429 Da

Linker TPSA

132.88 Å²

Linker xLogP

0.2019

ADCdb linker

LIN0ENDIF

In-vitro stability

Stability note

Inherited from VA-PBD class. Stein Blood 2018 PMID 29196412 Ph1 N=131 R/R AML at 40 mcg/kg RP2D does not tabulate explicit clinical acAb t½ in d in the open-access full text; engineered-Cys EC-mAb platform (Kung Sutherland Blood 2013) is more homogeneous than conventional Cys but not necessarily longer-t½

Payload

Payload & physicochemistry

Payload profile

Payload

SGD-1882

Class

PBD dimer

Mechanism

DNA cross-linker

Released catabolite

SGD-1882 (free PBD dimer; DNA interstrand cross-linker)

Mechanistic subtype

DNA-crosslinker-PBD

Stereochem / salt

Free base

Bystander

Partial

PAMPA rank

725.8 Da

XLogP3

3.9

logD₇.₄

2.5

TPSA

138 Å²

pKa

5 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C42H39N5O7

PubChem CID

45257190

ADCdb payload

PAY0AKDAM

CAS no.

1436390-64-5

Hydrophobicity · logD₇.₄

hydrophilic −2+2.5+4 lipophilic

Bioactivity note

ADCdb reports IC50 ~0.10 ng/mL in high-CD33-expressing AML cell lines (e.g., MV4-11) and primary AML samples, rising to >110 ng/mL (up to >5000 ng/mL) in CD33-low/negative lines, indicating CD33 target-dependent cytotoxicity. PBD-dimer payload acts as a DNA minor-groove cross-lin

Dosing & regimen

Dosing

RP2D dose

40 mcg/kg

Schedule

Q3W (or D1+D4 split)

Route

Fractionated

Yes

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

0 %

OAE grade 3+

0 %

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

None

Grading scale

CTCAE v4.03

Reversibility

Partial

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 · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

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

—

16.7%

n=6 · 33A peri-alloHSCT, AML

5 mcg/kg

IV q4w

7.7%

n=13 · 33A + azacitidine, untreated higher-risk MDS

—

7.14%

n=14 · A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoieti

—

5.26%

n=19 · Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine

10 mcg/kg

IV q4w

n=6 · 33A + azacitidine, untreated higher-risk MDS

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

vadastuximab-talirine

Approval status

Discontinued

Approval year

UniProt

P20138

ADCdb ADC

DRG0WXQJL

ADCdb antibody

ANI0MDDEU

ADCdb target

PATR0RIOXT

Primary source

Stein Blood 2018 PMID 29196412^{no such source}

Aliases & development codes

SGN-CD33A; anti-CD33 PBD

Notes

PBD on CD33 (like gemtuzumab calicheamicin); both 0% OAE. V3.1: 0% OAE supportable — Stein 2018 Blood has no ocular AEs. n=131 is total Ph1; 18 at 40 µg/kg RP2D.^{no such source}