Mirvetuximab soravtansine

FDA-approved

Elahere; IMGN853

Target

Folate receptor alpha · FOLR1

Sponsor

ImmunoGen/AbbVie

Indication

FOLR1+ ovarian cancer

Target family

GPI-anchored

RP2D dose

6 mg/kg AIBW

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

8 adverse-event terms

Ocular

Any-grade

59%

G3+

11%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

36%

Express.

0.02%

Limbus

Express.

0.07%

Conjunctiva

Express.

0.19%

Lens

Express.

Retina / RPE

Express.

3.21%

0.4 nTPM

Off-target signature

36% corneal toxicity, yet the Folate receptor alpha target is detected in only 0.02% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular adverse reactions59%

G3+ 11.3%n=682

Vision blurred50%

G3+ 7%n=106

Keratopathy37%

G3+ 9%n=106

Dry eye27%

G3+ 2%n=106

Cataract16%

G3+ 3%n=682

Photophobia14%

G3+ 0.5%n=682

Eye pain10%

n=682

Uveitis1%

n=106

Per-trial detail

Adverse events by trial

FORWARD I (NCT02631876)Phase 36 mg/kg AIBW IV Q3Wn=243CTCAE NRCto verify

CT.gov NCT02631876 all-cause mortality (derived G5; includes non-AE/PD deaths) NCT02631876

453 adverse-event terms · 23 systems · expand a system below

Ocular63

Vision blurred

42.8%

104/243

Keratopathy

31.7%

77/243

Dry eye

28%

68/243

Visual acuity reduced

21.4%

52/243

Cataract

14.8%

36/243

Photophobia

14%

34/243

Eye pain

12.8%G3+ 0.4%

31/243

Vitreous floaters

5.3%

13/243

Foreign body sensation in eyes

3.7%

9/243

Visual impairment

3.7%

9/243

Keratitis

3.3%

8/243

Eye irritation

2.9%

7/243

Lacrimation increased

2.5%

6/243

Corneal deposits

2.1%

5/243

Eye pruritus

2.1%

5/243

Ocular discomfort

2.1%

5/243

Punctate keratitis

1.6%G3+ 0.4%

4/243

Blepharitis

1.2%

3/243

Diplopia

1.2%

3/243

Glaucoma

1.2%

3/243

Photopsia

1.2%

3/243

Uveitis

1.2%

3/243

Asthenopia

0.8%

2/243

Chalazion

0.8%

2/243

Conjunctival haemorrhage

0.8%

2/243

Conjunctival hyperaemia

0.8%

2/243

Lacrimation decreased

0.8%

2/243

Metamorphopsia

0.8%

2/243

Ocular hyperaemia

0.8%

2/243

Xerophthalmia

0.8%

2/243

Abnormal sensation in eye

0.4%

1/243

Acquired corneal dystrophy

0.4%

1/243

Age-related macular degeneration

0.4%

1/243

Blepharochalasis

0.4%

1/243

Cataract nuclear

0.4%

1/243

Conjunctival irritation

0.4%

1/243

Corneal cyst

0.4%

1/243

Corneal oedema

0.4%

1/243

Dyschromatopsia

0.4%

1/243

Eye disorder

0.4%

1/243

Eye inflammation

0.4%

1/243

Eye swelling

0.4%

1/243

Eyelid oedema

0.4%

1/243

Eyelid pain

0.4%

1/243

Eyelid skin dryness

0.4%

1/243

Halo vision

0.4%

1/243

Hypermetropia

0.4%

1/243

Meibomianitis

0.4%

1/243

Myopia

0.4%

1/243

Night blindness

0.4%

1/243

Ocular hypertension

0.4%

1/243

Ocular toxicity

0.4%

1/243

Optic nerve disorder

0.4%

1/243

Papilloedema

0.4%

1/243

Periorbital oedema

0.4%

1/243

Pterygium

0.4%

1/243

Pupils unequal

0.4%

1/243

Retinal detachment

0.4%

1/243

Retinal drusen

0.4%

1/243

Retinopathy

0.4%

1/243

Sympathetic ophthalmia

0.4%

1/243

Trichiasis

0.4%

1/243

Vitreous detachment

0.4%

1/243

GI49

Infections43

Investigations37

Neurologic (other)28

Pulmonary28

General27

Injury25

Musculoskeletal25

Dermatologic22

Renal19

Metabolic16

Psychiatric14

Vascular11

Hematologic9

Other9

Neoplasms7

Ear6

Cardiac5

Hepatic5

Endocrine2

Immune2

Overall/Summary1

Construct

Molecular anatomy

Antibody

IgG1

Chimeric

Linker

Cleavable

3.4

DAR

Payload

DM4 (free)

Tubulin inhibitor

Linker structureC13H14N2O7S3

[H]OS(=O)(=O)C([H])(C(=O)ON1C(=O)C([H])([H])C([H])([H])C1=O)C([H])([H])C([H])([H])SSc1nc([H])c([H])c([H])c1[H]

Payload structureC38H54ClN3O10S

C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)C)\C)OC)(NC(=O)O2)O

Antibody

Antibody & Fc engineering

Antibody

M9346A

Isotype

IgG1

Origin

Chimeric

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

0.36

Linker & conjugation

Linker chemistry

Linker profile

Linker

SPDB / sulfo-SPDB

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (NHS sulfo-SPDB)

Symmetry

Asymmetric

DAR (mean)

3.4

DAR homogeneity

Heterogeneous

Plasma t½

4.8 d

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

Sulfonate

Cell line

Chinese Hamster Ovary

Formula

C13H14N2O7S3

Linker MW

406.463 Da

Linker TPSA

130.94 Å²

Linker xLogP

1.0756

ADCdb linker

LIN0MESCO

In-vitro stability

Stability note

Hindered disulfide; ADC t½ ~5–7 d (Pouzin 2022 mirvetuximab popPK); released DM4 undergoes S-methylation to S-Me-DM4 with formation-limited kinetics (Tu BJCP 2024 confirmed)

Payload

Payload & physicochemistry

Payload profile

Payload

DM4 (free)

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (S-methyl-DM4 is the predominant circulating active catabolite)

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Free thiol

Bystander

Yes

PAMPA rank

780.4 Da

XLogP3

3.2

logD₇.₄

TPSA

157 Å²

pKa

10.3 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C38H54ClN3O10S

PubChem CID

11686439

ADCdb payload

PAY0GTSVM

Plasma protein binding (%)

99 %

Hydrophobicity · logD₇.₄

hydrophilic −2+3+4 lipophilic

Bioactivity note

ADCdb-reported ADC potency (IC50): KB cells 0.15 +/- 0.08 nM; JEG-3 0.20 +/- 0.10 nM; IGROV-1 1.00 +/- 0.40 nM; END-2 0.20 ug/mL; END-1 74.6 ug/mL. Source: ADCdb DRG0GKOZH.

Dosing & regimen

Dosing

RP2D dose

6 mg/kg AIBW

Schedule

Q3W

Route

Fractionated

n at RP2D

682

Dose basis

Switched: TBW→AIBW

Trial phase

Approved

Dose-OAE available

Yes

Tox summary basis

RP2D

Pharmacology

Clinical pharmacokinetics

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

	Intact ADC	Free payload
Cmax	137.3µg/mL	4.1ng/mL
AUC	20.6h*mg/mL+1	530h*ng/mL+1
Tmax	end of infusion	~2days
t½	4.8days	2.8days
CL	19mL/hour	14L/hour
Vd	2.6L+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

59 %

OAE grade 3+

11 %

OAE data status

reported

Severity (weighted)

25.4

Keratopathy

36 %

Conjunctival

Dry eye

27 %

Blurred vision

48 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v5.0

Reversibility

Reversible

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

Cornea (central)

0.02 %

Cornea (limbal)

0.07 %

Conjunctiva

0.19 %

RPE

3.21 %

Retina (HPA)

0.4 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v5Denominator: RP2D

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

1.1 mg/kg

Weekly

20%

n=5 · First-in-Human IMGN853

1.8 mg/kg

Weekly

25%

n=4 · First-in-Human IMGN853

2.0 mg/kg

Weekly

22.2%

n=9 · First-in-Human IMGN853

2.5 mg/kg

Weekly

14.3%

n=7 · First-in-Human IMGN853

3.3 mg/kg

IV Q3W

11.1%

n=9 · First-in-Human IMGN853

5 mg/kg

IV Q3W

33.3%

n=3 · FORWARD II

5 mg/kg

IV Q3W

25%

n=4 · FORWARD II

5 mg/kg

IV Q3W

25%

n=4 · FORWARD II

5 mg/kg

IV Q3W

25%

n=4 · FORWARD II

5 mg/kg

IV Q3W

25%

n=4 · FORWARD II

5 mg/kg

IV Q3W

20%

n=5 · FORWARD II

5.0 mg/kg

IV Q3W

5.6%

n=18 · First-in-Human IMGN853

6 mg/kg AIBW

Q3W

59%

n=682 · Pooled safety population (Studies 0416/0417/0403/0401)

6 mg/kg AIBW

IV Q3W (Day 1 of 21-day cycle)

37%

n=218 · MIRASOL (Study 0416) [label]

6 mg/kg AIBW

IV Q3W (Day 1 of 21-day cycle)

37%

n=106 · SORAYA (Study 0417) [label]

6 mg/kg AIBW

Q3W

37%

n=218 · MIRASOL (Study 0416)

6 mg/kg AIBW

Q3W

37%

n=106 · SORAYA (Study 0417)

6 mg/kg AIBW

Q3W

36%

n=682 · Pooled safety population (Studies 0416/0417/0403/0401)

6 mg/kg AIBW

IV Q3W

34.4%

n=227 · MIRASOL

6 mg/kg

IV Q3W

33.3%

n=3 · TAK-853 / mirvetuximab

6 mg/kg AIBW

IV Q3W

32.1%

n=106 · SORAYA

6 mg/kg AIBW

IV Q3W

31.7%

n=243 · FORWARD I

6 mg/kg

IV Q3W

29.4%

n=126 · FORWARD II

6.0 mg/kg

IV Q3W

14.3%

n=7 · First-in-Human IMGN853

6 mg/kg

IV Q3W

12%

n=25 · TAK-853 / mirvetuximab

6 mg/kg

IV Q3W

10%

n=10 · FORWARD II

6 mg/kg AIBW

IV Q3W

6.3%

n=79 · Mirvetuximab platinum-sensitive

6 mg/kg

IV Q3W

1.8%

n=56 · FORWARD II

6 mg/kg

n=106

7.0 mg/kg

IV Q3W

20%

n=5 · First-in-Human IMGN853

IV Q3W (Day 1 of 21-day cycle)

50%

n=2 · Mirvetuximab in TNBC

IV Q3W

48.8%

n=41 · FORWARD II

IV Q3W

29.2%

n=65 · Mirvetuximab + SL-172154

IV Q3W

11.1%

n=18 · IMGN853 + Pembrolizumab endometrial

IV Q3W

6.5%

n=46 · First-in-Human IMGN853

IV Q3W

4.2%

n=24 · First-in-Human IMGN853

IV Q3W

3.7%

n=27 · First-in-Human IMGN853

IV Q3W

2.5%

n=40 · First-in-Human IMGN853

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

mirvetuximab-soravtansine

Approval status

FDA-approved

Approval year

2022

UniProt

P15328

ADCdb ADC

DRG0GKOZH

ADCdb antibody

ANI0VPFFS

ADCdb target

TAR0QHAVI

Primary source

ELAHERE PI Section 6.1; SORAYA JCO 2023; MIRASOL NEJM 2023

Aliases & development codes

Elahere; IMGN853

Notes

FOLR1 absent from cornea; OAE is DM4 bystander via cleavable disulfide. V3.1: origin corrected Humanized→Chimeric per ELAHERE label §11.