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

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%

Per-trial detail

Adverse events by trial

CARMEN-LC03 (NCT04154956)Phase 3100 mg/m^2 IV Q2Wn=194CTCAE MedDRA 26.0B

CT.gov posted results NCT04154956 (serious AE; 1/194; MedDRA 26.0) NCT04154956

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

Infections10

Pneumonia

1.55%

3/194

Covid-19

1.03%

2/194

Gastrointestinal Infection

0.52%

1/194

Infection

0.52%

1/194

Infectious Pleural Effusion

0.52%

1/194

Pneumocystis Jirovecii Pneumonia

0.52%

1/194

Pneumonia Influenzal

0.52%

1/194

Respiratory Tract Infection

0.52%

1/194

Upper Respiratory Tract Infection

0.52%

1/194

Urinary Tract Infection

0.52%

1/194

Neurologic (other)9

Pulmonary8

General5

GI3

Investigations3

Musculoskeletal3

Ocular2

Dry Eye

0.52%

1/194

Uveitis

0.52%

1/194

Hepatic2

Injury2

Metabolic2

Neoplasms2

Psychiatric2

Renal2

Vascular2

Hematologic1

Cardiac1

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

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

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

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%

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)

100 mg/m^2

IV Q2W

0.52%

n=194 · CARMEN-LC03

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)

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

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.