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

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

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

5.5 d

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

Sulfonate

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

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

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

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

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

Ascertainment: Systematic eye examsScale: CTCAE v5Denominator: RP2D

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.