Belantamab mafodotin

FDA-approved

Blenrep; GSK2857916; J6M0-mcMMAF

Target

BCMA · TNFRSF17

Sponsor

GSK

Indication

BCMA+ multiple myeloma

Target family

TNF receptor superfamily

RP2D dose

2.5 mg/kg

Q3W (extend to Q6W for events)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

20 adverse-event terms

Ocular

Any-grade

92%

G3+

77%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

86%

Express.

0.4%

Limbus

Express.

0.6%

Conjunctiva

Express.

0.06%

Lens

Express.

Retina / RPE

Express.

0.1 nTPM

Off-target signature

86% corneal toxicity, yet the BCMA target is detected in only 0.4% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Visual acuity reduced (BCVA reduction)89%

G3+ 57%n=242

Ocular events (composite, eye-exam based)89%

G3+ 43%

Corneal exam findings (keratopathy)86%

G3+ 72%n=242

Reduction in BCVA to 20/50 or worse (in >=1 eye)69%

Vision blurred66%

G3+ 22%n=242

Dry eye51%

G3+ 7%n=242

Photophobia47%

G3+ 2%n=242

Foreign body sensation in eyes44%

G3+ 3%n=242

Eye irritation43%

G3+ 5%n=242

Eye pain33%

G3+ 0.8%n=242

Cataract24%

G3+ 8%n=242

Punctate keratitis22.7%

Corneal epithelial microcysts (microcyst-like deposits)22.7%

Visual impairment11%

G3+ 5%n=242

Corneal opacity8.7%

Lacrimation increased6%

Keratitis5.3%

Corneal ulcer (incl. with infection)-

Eye pruritus-

Diplopia-

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 structureC39H65N5O8

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)NC

Antibody

Antibody & Fc engineering

Antibody

J6M0 (belantamab)

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Afucosylated

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

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

13.0 d

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

None

Formula

C10H13NO4

Linker MW

211.217 Da

Linker TPSA

74.68 Å²

Linker xLogP

0.5564

ADCdb linker

LIN0TAFAV

In-vitro stability

Stability note

acAb t½ 11.5 d after dose 1 → 14.3 d at steady state (Rathi 2021 popPK N=380 DREAMM-2 + DREAMM-1); recent integrated popPK across DREAMM-1/-2/-3/-7/-8 (Ferron-Brady 2025) reports initial t½ 13.0 d → SS 16.8 d (mono) / 19.1 d (combo). Released cys-mcMMAF t½ 10 min–14 h (rapid).

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

C39H65N5O8

PubChem CID

10395173

ADCdb payload

PAY0QLDVX

Hydrophobicity · logD₇.₄

hydrophilic −2-1+4 lipophilic

Bioactivity note

ADCdb (DRG0NDXRU) reports a cell-based EC50 of 30.6 ug/mL on EL4 cells (moderate BCMA expression) and Phase 1 clinical efficacy (ORR 60% at 3.4 mg/kg; median PFS 12 months; median DoR 14.3 months). MMAF is an antimitotic tubulin-polymerization inhibitor.

Dosing & regimen

Dosing

RP2D dose

2.5 mg/kg

Schedule

Q3W (extend to Q6W for events)

Route

Fractionated

n at RP2D

242

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

92 %

OAE grade 3+

77 %

OAE data status

reported

Severity (weighted)

81.5

Keratopathy

86 %

Conjunctival

Dry eye

51 %

Blurred vision

66 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

Other

Reversibility

Reversible

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

Cornea (central)

0.4 %

Cornea (limbal)

0.6 %

Conjunctiva

0.06 %

RPE

0 %

Retina (HPA)

0.1 nTPM

Cross-trial comparability

Ascertainment: Systematic eye examsScale: OtherDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

belantamab-mafodotin

Approval status

FDA-approved

Approval year

2020

UniProt

Q02223

ADCdb ADC

DRG0NDXRU

ADCdb antibody

ANI0MSWWH

ADCdb target

TNFRSF17

Primary source

BLENREP PI Section 6.1 / DREAMM-7 (G3/4 77%)

Aliases & development codes

Blenrep; GSK2857916; J6M0-mcMMAF

Notes

Dose-OAE data: DREAMM-1/-2/-7/-8/-14/Q6W extension; charged Cys-mcMMAF catabolite trapped by macropinocytosis in corneal basal cells