Tusamitamab ravtansine

Discontinued

SAR408701; huMAb2-3-SPDB-DM4

Target

CEACAM5 (CEA) · CEACAM5

Sponsor

Sanofi

Indication

CEACAM5+ NSCLC

Target family

CEA family / 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

19 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=50

Corneal events (composite, any corneal TEAE)25.8%

G3+ 6.7%

Keratopathy15.2%

G3+ 2.2%n=50

Visual Acuity Reduced12.28%

non-seriousn=57

Dry Eye10%

non-seriousn=50

Vision Blurred10%

non-seriousn=50

Lacrimation Increased7.02%

non-seriousn=57

Conjunctivitis Allergic7.02%

non-seriousn=57

Cataract5.7%

n=371

Dry eye5.7%

n=371

Punctate Keratitis5.26%

non-seriousn=57

Visual Impairment3.51%

non-seriousn=57

Conjunctivitis2%

non-seriousn=50

Diabetic Retinopathy2%

non-seriousn=50

Eye Pruritus2%

non-seriousn=50

Xerophthalmia2%

non-seriousn=50

Superior limbic keratoconjunctivitis1.1%

n=92

Lacrimation increased1%

n=371

Per-trial detail

Adverse events by trial

CARMEN-LC05PHASE2real-worldn=57CTCAE NR (ClinicalTrials.govPooledC

ClinicalTrials.gov NCT04524689 posted results, adverse events module (non-serious; 1/57 pooled across arms)

94 adverse-event terms · 18 systems · expand a system below

GI13

Diarrhoea

29.82%non-serious

17/57

Nausea

29.82%non-serious

17/57

Vomiting

17.54%non-serious

10/57

Constipation

15.79%non-serious

9/57

Abdominal Pain

5.26%non-serious

3/57

Dry Mouth

3.51%non-serious

2/57

Dyspepsia

3.51%non-serious

2/57

Dysphagia

3.51%non-serious

2/57

Gastrooesophageal Reflux Disease

3.51%non-serious

2/57

Odynophagia

3.51%non-serious

2/57

Gastritis

1.75%non-serious

1/57

Haematochezia

1.75%non-serious

1/57

Tongue Blistering

1.75%non-serious

1/57

Pulmonary13

Ocular10

Keratitis

28.07%non-serious

16/57

Dry Eye

12.28%non-serious

7/57

Vision Blurred

12.28%non-serious

7/57

Visual Acuity Reduced

12.28%non-serious

7/57

Cataract

10.53%non-serious

6/57

Conjunctivitis Allergic

7.02%non-serious

4/57

Keratopathy

7.02%non-serious

4/57

Lacrimation Increased

7.02%non-serious

4/57

Punctate Keratitis

5.26%non-serious

3/57

Visual Impairment

3.51%non-serious

2/57

General8

Infections7

Neurologic (other)7

Dermatologic6

Musculoskeletal5

Hematologic4

Vascular4

Endocrine3

Investigations3

Psychiatric3

Injury2

Other2

Renal2

Ear1

Metabolic1

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^inferred

Glycoengineering

Standard^inferred

Effector silencing

None^inferred

FcγR binding

Retained

C1q binding

Retained^inferred

Target KD (nM)

0.017

Epitope / domain

A3-B3 extracellular domain of CEACAM5

Linker & conjugation

Linker chemistry

Linker profile

Linker

SPDB

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (NHS SPDB)

Symmetry

Asymmetric

DAR (mean)

3.8

DAR homogeneity

Heterogeneous

Plasma t½

8.8 d

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C13H14N2O4S2

Linker MW

326.399 Da

Linker TPSA

127.17 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.^contradicted

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

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

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 1

Dose-OAE available

Yes

Tox summary basis

RP2D

ADA rate (%)

8.7 %

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 v4.03

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: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D

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

100 mg/m^2

IV Q2W

38%

n=92 · NCT02187848 FIH - NSQ NSCLC dose-expansion (high/moderate CEACAM5)

80-100 mg/m^2

IV Q2W

33.3%

n=9 · NCT03324113 (Japanese phase 1, advanced solid tumours)

100 mg/m2

Q2W

29.3%

n=92 · NCT02187848 (NSq NSCLC dose-expansion)

100 mg/m2

25.8%

100 mg/m^2 (170 mg/m^2 C1 loading)

IV Q2W; 170 mg/m^2 loading C1D1 then 100 mg/m^2 Q2W

16.67%

n=6 · NCT04659603 (CEACAM5+ advanced solid tumors)

100 mg/m^2

IV Q2W

13.64%

n=22 · NCT05245071 (NSQ NSCLC, neg/moderate CEACAM5 + high CEA)

100 mg/m^2 (170 loading) + gemcitabine 1000 mg/m^2

tusamitamab IV Q2W + gemcitabine D1,8,15 Q4W

12.5%

n=16 · NCT04659603 (CEACAM5+ advanced solid tumors)

100 mg/m^2

IV Q2W

10.82%

n=194 · CARMEN-LC03

100 mg/m^2 (170 loading) + ramucirumab 8 mg/kg

IV Q2W

8.57%

n=35 · NCT05071053 (gastric/GEJ cancer + ramucirumab)

100 mg/m2

6.7%

n=371

100 mg/m^2 + ramucirumab 8 mg/kg

IV Q2W

6.45%

n=31 · CARMEN-LC04

100 mg/m^2 (170 mg/m^2 C1 loading)

IV Q2W; 170 mg/m^2 loading C1D1 then 100 mg/m^2 Q2W

3.57%

n=28 · NCT04659603 (CEACAM5+ advanced solid tumors)

150 mg/m^2 + pembrolizumab 200 mg

IV Q3W (doublet, Part A)

43.48%

n=23 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

150 mg/m^2 + pembrolizumab 200 mg + platinum + pemetrexed 500 mg/m^2

IV Q3W (quadruplet, Part C)

18.18%

n=22 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

150 mg/m^2 + pembrolizumab 200 mg + cisplatin 75 / carboplatin AUC5

IV Q3W (triplet, Part B)

16.67%

n=6 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

170 mg/m^2 + pembrolizumab 200 mg + cisplatin 75 / carboplatin AUC5

IV Q3W (triplet, Part B)

100%

n=1 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

135-170 mg/m^2 C1 loading then 100 mg/m^2

IV Q2W with C1 loading

56.3%

n=16 · NCT03324113 (Japanese phase 1, advanced solid tumours)

170 mg/m^2 + pembrolizumab 200 mg

IV Q3W (doublet, Part A)

50%

n=2 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

170 mg/m^2 + pembrolizumab 200 mg + platinum + pemetrexed 500 mg/m^2

IV Q3W (quadruplet, Part C)

33.33%

n=3 · NCT04524689 (NSQ NSCLC + pembrolizumab combinations)

120-170 mg/m^2 C1 loading then 100 mg/m^2

IV Q2W with C1 loading dose

32.1%

n=28 · NCT02187848 FIH - alternative dosing escalation (Q2W-LD / Q3W)

120-190 mg/m^2

IV Q3W

40%

n=15 · NCT02187848 FIH - alternative dosing escalation (Q2W-LD / Q3W)

—

28.07%

n=57 · CARMEN-LC05

—

10.82%

n=194 · CARMEN-LC03

—

n=50 · CARMEN-BT01

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

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^{no such source}

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.^{no such source}