Tusamitamab ravtansine

Discontinued

SAR408701; huMAb2-3-SPDB-DM4

Target

CEACAM5 (CEA) · CEACAM5

Sponsor

Sanofi

Indication

CEACAM5+ NSCLC

Target family

Nectin / Ig-CAM

RP2D dose

100 mg/m² Q2W

Q2WRP2D

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

38%

G3+

12%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

29.3%

Express.

0.03%

Limbus

Express.

0.7%

Conjunctiva

Express.

10.55%

Lens

Express.

Retina / RPE

Express.

0 nTPM

Off-target signature

29.3% corneal toxicity, yet the CEACAM5 (CEA) target is detected in only 0.03% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Corneal disorder (any corneal TEAE, composite)38%

G3+ 12%n=92

Keratitis29.3%

G3+ 10.9%n=92

Corneal events (composite, any corneal TEAE)25.8%

G3+ 6.7%

Keratopathy15.2%

G3+ 2.2%n=92

Cataract5.7%

Dry eye5.7%

Superior limbic keratoconjunctivitis1.1%

n=92

Lacrimation increased1%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

3.8

DAR

Payload

DM4 (free)

Tubulin inhibitor

Linker structureC13H14N2O4S2

[H]c1nc(SSC([H])([H])C([H])([H])C([H])([H])C(=O)ON2C(=O)C([H])([H])C([H])([H])C2=O)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

huMAb2-3 (tusamitamab)

Isotype

IgG1

Origin

Humanized

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 SPDB)

Symmetry

Asymmetric

DAR (mean)

3.8

DAR homogeneity

Heterogeneous

Plasma t½

7.0 d

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C13H14N2O4S2

Linker MW

326.399 Da

Linker TPSA

76.57 Å²

Linker xLogP

2.2093

ADCdb linker

LIN0VZYER

In-vitro stability

Stability note

Two reports converge: terminal t½ 6 d (range 6–8 d) per Gazzah Ann Oncol 2022 FIH; semi-mech popPK (Sun JPP 2022) reports 8.8 d for conjugated Ab and 12.2 d for naked antibody. Midpoint 7 d. Hindered disulfide; DM4 catabolite undergoes S-methylation.

Payload

Payload & physicochemistry

Payload profile

Payload

DM4 (free)

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (MeDM4)

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

ADC IC50 (cytotoxicity): 0.20 +/- 0.04 nM and 0.38 +/- 0.07 nM in HPAF-II pancreatic ductal adenocarcinoma cells; 1.08 +/- 0.17 nM in MKN45 gastric adenocarcinoma cells (ADCdb DRG0ELYWP). Free DM4 payload IC50 ~1 nM (Hep-G2), ~10 nM (Lu1) per ADCdb payload page PAY0GTSVM.

Dosing & regimen

Dosing

RP2D dose

100 mg/m² Q2W

Schedule

Q2W

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Phase 2

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

38 %

OAE grade 3+

12 %

OAE data status

reported

Severity (weighted)

19.8

Keratopathy

29.3 %

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4

Reversibility

Reversible

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

Cornea (central)

0.03 %

Cornea (limbal)

0.7 %

Conjunctiva

10.55 %

RPE

0 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

tusamitamab-ravtansine

Approval status

Discontinued

Approval year

UniProt

P06731

ADCdb ADC

DRG0ELYWP

ADCdb antibody

ANI0IYDRE

ADCdb target

TAR0CXRBX

Primary source

Gazzah JTO Clin Res Rep 2025; PMC12478256

Aliases & development codes

SAR408701; huMAb2-3-SPDB-DM4

Notes

G3+ 12% = 11/92 (CEACAM5 essentially absent from cornea). V3.1: RP2D corrected 170→100 mg/m² Q2W per Gazzah Ann Oncol 2022 MTD (used in CARMEN-LC03 Phase 3). 170 mg/m² not a known tusamitamab dose.