Glembatumumab vedotin

Discontinued

CDX-011; CR011-vcMMAE

Target

GPNMB · GPNMB

Sponsor

Celldex

Indication

GPNMB+ TNBC/melanoma

Target family

Other

RP2D dose

1.88 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

2 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

1.48%

Limbus

Express.

11.06%

Conjunctiva

Express.

49.3%

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

Vision Blurred4.55%

non-seriousn=132

Eye Infection1.52%

non-seriousn=132

Per-trial detail

Adverse events by trial

A Study of Glembatumumab Vedotin as Monotherapy or in Combination With ImmunothePHASE2real-worldn=132CTCAE NR (ClinicalTrials.govPooledC

ClinicalTrials.gov NCT02302339 posted results, adverse events module (non-serious; 32/132 pooled across arms)

117 adverse-event terms · 19 systems · expand a system below

Dermatologic16

Alopecia

47.73%non-serious

63/132

Pruritus

28.79%non-serious

38/132

Rash Maculo-Papular

28.79%non-serious

38/132

Rash

12.88%non-serious

17/132

Rash Generalised

11.36%non-serious

15/132

Pruritis Generalised

9.85%non-serious

13/132

Erythema

6.06%non-serious

8/132

Rash Pruritic

4.55%non-serious

6/132

Rash Erythaemous

3.79%non-serious

5/132

Rash Mascular

3.79%non-serious

5/132

Vitiligo

3.79%non-serious

5/132

Dry Skin

3.03%non-serious

4/132

Skin Hyperpigmentation

3.03%non-serious

4/132

Night Sweats

2.27%non-serious

3/132

Decubitus Ulcer

1.52%non-serious

2/132

Skin Discolouration

0.76%non-serious

1/132

GI15

Metabolic13

General10

Musculoskeletal9

Investigations8

Neurologic (other)8

Pulmonary6

Infections5

Psychiatric5

Hematologic4

Cardiac4

Injury3

Renal3

Ocular2

Vision Blurred

4.55%non-serious

6/132

Eye Infection

1.52%non-serious

2/132

Other2

Vascular2

Endocrine1

Hepatic1

Construct

Molecular anatomy

Antibody

IgG2

Human

Linker

Cleavable

4.5

DAR

Payload

MMAE

Tubulin inhibitor

Linker structureC28H40N6O7

[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=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])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H])c([H])c1[H]

Payload structureC39H67N5O7

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

anti-GPNMB (glembatumumab)

Isotype

IgG2

Origin

Human

Fc modifications

None^inferred

Glycoengineering

Standard^inferred

Effector silencing

None

FcγR binding

Retained

C1q binding

Reduced^inferred

Dev code

CR011

Linker & conjugation

Linker chemistry

Linker profile

Linker

MC-vc-PAB (vedotin)

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric^silent

DAR (mean)

4.5

DAR homogeneity

Heterogeneous

Plasma t½

1 d

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Stability note

Conventional MC-vc-PAB on IgG2 inter-chain Cys (DAR 4.5). Roth Pediatr Blood Cancer 2020 PMC6952063 (osteosarcoma) reports acAb t½ 17.3–36.8 h (range across 3 patients aged 12–14) — implying ~1 d in pediatric population, but small N and pediatric body composition makes extrapolation to adult cohort unreliable. Adult preclinical t½ in mouse 5.5–10.8 d at 1 mg/kg (Doolittle 2019). Adult clinical t½ in METRIC TNBC / EMERGE not separately tabulated in open Yardley 2015 / Ott 2019 publications

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

ADCdb (DRG0IRZIB) reports clinical/preclinical outcomes: objective response rates ~11-12% in melanoma and breast cancer trials; partial response 7.69% in lung cancer; tumor growth inhibition ~93.33% in xenograft models. No discrete payload IC50 value listed on the ADCdb ADC page.

Dosing & regimen

Dosing

RP2D dose

1.88 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 2

Dose-OAE available

Tox summary basis

RP2D

ADA rate (%)

12 %

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^ambiguous

Grading scale

CTCAE v4.0

Reversibility

Unknown^ambiguous

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

Cornea (central)

1.48 %

Cornea (limbal)

11.06 %

Conjunctiva

49.3 %

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

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

1.9 mg/kg + anti-PD-1

IV q3w (Day 1 of 21-day cycle)

6.9%

n=29 · Glembatumumab vedotin advanced melanoma

1.9 mg/kg

IV q3w (Day 1 of 21-day cycle)

4.8%

n=62 · Glembatumumab vedotin advanced melanoma

1.9 mg/kg + varlilumab

IV q3w (Day 1 of 21-day cycle)

2.9%

n=34 · Glembatumumab vedotin advanced melanoma

1.3-2.2 mg/kg (dose-escalation)

IV 90-min q3w (Day 1 of 21-day cycle)

7.7%

n=13 · Glembatumumab vedotin lung SCC

—

4.55%

n=132 · A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunothe

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

glembatumumab-vedotin

Approval status

Discontinued

Approval year

2018

UniProt

Q14956

ADCdb ADC

DRG0IRZIB

ADCdb antibody

ANI0PYFAC

ADCdb target

TAR0MCXEX

Primary source

Ott Cancer 2019; Yardley npj BC 2021^{no such source}

Aliases & development codes

CDX-011; CR011-vcMMAE

Notes

Unexplained 0% OAE despite 49.3% conjunctival expression - MMAE outlier. V3.1: IgG2 isotype CONFIRMED (XenoMouse fully human). DAR 4.5 may be high — commonly 3.8-4 for vc-MMAE; flagged for v3.2.^{no such source}