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-

Per-trial detail

Adverse events by trial

DREAMM-5 sub (Niro+Pom) (NCT07150104)Phase 1/Phase 2see armn=14B

CT.gov posted results NCT07150104 (non-serious AE; 1/14; MedDRA v28.0) NCT07150104

119 adverse-event terms · 17 systems · expand a system below

Ocular17

Dry eye

35.71%

5/14

Vision blurred

35.71%

5/14

Eye pain

28.57%

4/14

Foreign body sensation in eyes

28.57%

4/14

Eye irritation

21.43%

3/14

Cataract

14.29%

2/14

Conjunctival hyperaemia

7.14%

1/14

Corneal neovascularisation

7.14%

1/14

Ectropion

7.14%

1/14

Epiretinal membrane

7.14%

1/14

Eye allergy

7.14%

1/14

Keratitis

7.14%

1/14

Macular degeneration

7.14%

1/14

Macular telangiectasia

7.14%

1/14

Photophobia

7.14%

1/14

Visual acuity reduced

7.14%

1/14

Vitreous floaters

7.14%

1/14

Investigations14

Infections12

Musculoskeletal12

Metabolic10

GI9

Dermatologic9

General6

Neurologic (other)6

Injury4

Renal4

Pulmonary4

Neoplasms3

Psychiatric3

Vascular3

Hematologic2

Hepatic1

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

Target KD (nM)

1.61

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

Cell line

CHO

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

Plasma protein binding (%)

70 %

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

ADA rate (%)

3 %

Pharmacology

Clinical pharmacokinetics

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

	Intact ADC	Total antibody	Free payload
Cmax	43.7mcg/mL+1	—	0.976ng/mL+1
AUC	3950mcg*h/mL+2	—	94.2ng*h/mL+1
Tmax	at or shortly after end of infusionh (30-min infusion)+1	at or shortly after end of infusionh (30-min infusion)	22.83h
t½	13days+3	—	—
CL	0.901L/day+3	—	—
Vd	10.8L+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

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 (KVA)

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 · source-verified

Ascertainment: Systematic eye examsScale: OtherDenominator: RP2D⚠ Not comparable: non-CTCAE grading scale

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

0.12 mg/kg

25%

n=4 · DREAMM-1

0.24 mg/kg

25%

n=4 · DREAMM-1

0.48 mg/kg

25%

n=4 · DREAMM-1

0.95 mg/kg

20%

n=10 · DREAMM-5 sub (Nirogacestat)

0.95 mg/kg

Q3W

5.88%

n=34 · DREAMM-5 sub (Nirogacestat)

0.96 mg/kg

33.33%

n=3 · DREAMM-1

1.0 mg/kg

40%

n=10 · DREAMM-5 sub (Niro+Len+Dex)

1.0 mg/kg

Q4W

10%

n=10 · DREAMM-5 sub (Nirogacestat)

1.4 mg/kg

Q4W

40%

n=10 · DREAMM-5 sub (Nirogacestat)

1.4 mg/kg

Q8W

40%

n=10 · DREAMM-5 sub (Isatuximab)

1.9 mg/kg

75%

n=12 · DREAMM-6

1.9 mg/kg

50%

n=4 · DREAMM-5 sub (Dostarlimab)

1.9 mg/kg

33.33%

n=6 · DREAMM-5 sub (OX40/GSK1)

1.9 mg/kg

Q8W

30%

n=10 · DREAMM-5 sub (Isatuximab)

1.9 mg/kg

25%

n=4 · DREAMM-5 sub (Nirogacestat)

1.9 mg/kg

25%

n=4 · DREAMM-6

1.9 mg/kg

22.22%

n=9 · DREAMM-5 sub (Feladilimab)

1.9 mg/kg

8.33%

n=12 · DREAMM-6

1.9 mg/kg

8.33%

n=12 · DREAMM-6

1.9 mg/kg

Q6W

5.88%

n=17 · DREAMM-14 / alt-dosing

1.9 mg/kg

Q3W

n=40 · DREAMM-14 / alt-dosing

1.92 mg/kg

25%

n=4 · DREAMM-1

1.92 mg/kg

25%

n=4 · DREAMM-1

2.5 mg/kg

100%

n=6 · DREAMM-4

2.5 mg/kg

92.31%

n=13 · DREAMM-6

2.5 mg/kg

89%

2.5 mg/kg

Q3W, with bortezomib + dexamethasone

86%

n=242 · DREAMM-7

2.5 mg/kg (cycle 1) then 1.9 mg/kg

IV Q3W (with bortezomib+dexamethasone)

86%

n=242 · DREAMM-7

2.5 mg/kg

70.53%

n=95 · DREAMM-2

2.5 mg/kg

66.67%

n=3 · DREAMM-5 sub (OX40/GSK1)

2.5 mg/kg

Q6WEEKS

46.15%

n=39 · DREAMM-14 / alt-dosing

2.5 mg/kg

Q3W

37.84%

n=37 · DREAMM-5 sub (Nirogacestat)

2.5 mg/kg

25%

n=4 · Japanese dose-escalation (117159)

2.5 mg/kg

16.67%

n=6 · DREAMM-5 sub (Feladilimab)

2.50 mg/kg

12.5%

n=8 · DREAMM-1

2.5 mg/kg

10%

n=10 · DREAMM-5 sub (Feladilimab)

2.5 mg/kg

8.33%

n=12 · DREAMM-6

2.5 mg/kg

8.33%

n=12 · DREAMM-6

2.5 mg/kg

7.69%

n=13 · DREAMM-6

2.5 mg/kg

6.25%

n=16 · DREAMM-6

2.5 mg/kg

5.56%

n=18 · DREAMM-6

2.5 mg/kg

5.56%

n=18 · DREAMM-6

2.5 mg/kg

1.05%

n=95 · DREAMM-2

3.4 mg/kg

85.71%

n=7 · DREAMM-4

3.4 mg/kg

83.33%

n=12 · DREAMM-6

3.40 mg/kg

33.33%

n=3 · DREAMM-1

3.4 mg/kg

30.3%

n=99 · DREAMM-2

3.4 mg/kg

25%

n=4 · Japanese dose-escalation (117159)

3.40 mg/kg

16.67%

n=6 · DREAMM-1

3.40 mg/kg

8.57%

n=35 · DREAMM-1

3.4 mg/kg

6.25%

n=16 · DREAMM-6

3.4 mg/kg

4.17%

n=24 · DREAMM-2

3.40 mg/kg

2.86%

n=35 · DREAMM-1

4.60 mg/kg

16.67%

n=6 · DREAMM-1

see arm

100%

n=1 · Post-CAR-T maintenance

see arm

100%

n=3 · Bela+Cyclophosphamide+Dex

see arm

93.33%

n=30 · Real-world care-patterns (RWD)

see arm

90%

n=10 · DREAMM-8 (Japan)

see arm

70%

n=10 · DREAMM-7 (Japan expansion)

—

69%

see arm

66.12%

n=242 · DREAMM-7

see arm

50%

n=30 · DREAMM-7 (China subpop)

—

43%

see arm

Q3WEEKS

41.03%

n=39 · DREAMM-14 / alt-dosing

see arm

33.33%

n=6 · Hepatic-impairment PK (207497)

see arm

33.33%

n=3 · Bela+Cyclophosphamide+Dex

see arm

30%

n=10 · Plasmablastic/ALK+ LBCL

see arm

25%

n=4 · Bela+Cyclophosphamide+Dex

see arm

25%

n=4 · Japanese dose-escalation (117159)

see arm

22.67%

n=150 · DREAMM-8

see arm

10%

n=10 · DREAMM-5 sub (Niro+Len+Dex)

see arm

Q4W

10%

n=10 · DREAMM-5 sub (Isatuximab)

see arm

10%

n=30 · DREAMM-7 (China subpop)

see arm

10%

n=10 · DREAMM-7 (Japan expansion)

see arm

10%

n=10 · Plasmablastic/ALK+ LBCL

—

8.7%

see arm

7.14%

n=14 · DREAMM-5 sub (Niro+Pom)

—

see arm

5.53%

n=217 · DREAMM-3

see arm

Q3WEEKS

2.56%

n=39 · DREAMM-14 / alt-dosing

see arm

0.67%

n=150 · DREAMM-8

see arm

0.41%

n=242 · DREAMM-7

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

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