Cantuzumab ravtansine

Discontinued

IMGN242; IMGN-242; huC242-DM4; C242-DM4; C-242 DM4; cantuzumab ravtansine; CAS 868747-45-9; UNII RNQ8JQ4R9P

Target

CanAg (CA242), a sialylated carbohydrate epitope on MUC1 · MUC1

Sponsor

ImmunoGen

Indication

CanAg+ gastric / gastroesophageal junction cancer

Target family

Mucin

RP2D dose

168 mg/m²

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

0%severity100%

Assessed · clear

true 0%

No data

never assessed

4 adverse-event terms

Ocular

Any-grade

50%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular toxicity (drug-related; unspecified eye disorders)50%

Keratitis6.7%

Corneal deposits6.7%

Visual acuity reduced6.7%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

3.5

DAR

Payload

DM4

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

huC242 (cantuzumab)

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

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (SPDB / NHS ester)

Symmetry

Symmetric

DAR (mean)

3.5

DAR homogeneity

Heterogeneous

Plasma t½

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

Payload

Payload & physicochemistry

Payload profile

Payload

DM4

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (S-methyl-DM4 predominant circulating catabolite; Lys-Nepsilon-SPDB-DM4 primary lysosomal 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 (DRG0XCWMD): tumor growth inhibition approximately 48.85% in MOLP-8 xenograft at day 20; clinically well tolerated at 168 mg/m2 dose level (Phase 2, terminated). Free DM4 mechanism: tubulin-binding maytansinoid that inhibits microtubule assembly, causing mitotic block and a

Dosing & regimen

Dosing

RP2D dose

168 mg/m²

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Phase 2

Dose-OAE available

Yes

Tox summary basis

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

50 %

OAE grade 3+

OAE data status

reported

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

Reversibility

Reversible

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

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability

Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

cantuzumab-ravtansine

Approval status

Discontinued

Approval year

UniProt

P15941

ADCdb ADC

DRG0XCWMD

ADCdb antibody

ANI0KQQRV

ADCdb target

TAR0BWSFH

Primary source

Eaton 2015 ADC ocular-AE review (PMC4677113); huC242-DM4 Ph1 (Mita, JCO 2007;25(18_suppl):3062 / MCT 2007;6(11_suppl):B70) & IMGN242 Ph2 (ASCO 2009, JCO 27:15_suppl:e15625)

Aliases & development codes

IMGN242; IMGN-242; huC242-DM4; C242-DM4; C-242 DM4; cantuzumab ravtansine; CAS 868747-45-9; UNII RNQ8JQ4R9P

Notes

DM4 maytansinoid ADC (huC242-DM4 / IMGN242); DISTINCT from DM1 cantuzumab mertansine (SB-408075). Target CanAg = CA242, a sialylated carbohydrate epitope on MUC1 (ADCdb and ADC Review map the target gene to MUC1). MTD = RP2D = 168 mg/m² (BSA dosing in mg/m², NOT mg/kg); single IV infusion Q3W. OCULAR TOXICITY was the primary dose-limiting toxicity: Ph1 (n=30, doses 18-297 mg/m²) — 2/30 (6.7%) ocular DLTs (decreased visual acuity, corneal deposits, keratitis) at 223 mg/m² i.e. 2/6 within that above-MTD cohort, cycle 2, reversible (resolved in 1, markedly improved in the other) with lubricating drops; Ph2 gastric/GEJ Study 102 — 3/6 (50%) drug-related ocular toxicities in the first 6 pts at 168 mg/m². Ocular tox correlated with LOW plasma CanAg (<1000 U/mL, driving higher ADC exposure); protocol amended to CanAg-based dosing (126 vs 168 mg/m²), after which 0/3 pts had ocular tox. 'No clinically significant myelosuppression' and no HAHA/HADA -> hematologic columns left blank (not a documented 0). Ph1 had 12 grade 3/4 drug-related AEs (full breakdown not public) incl. 1 grade 3 diarrhea+dehydration at 168 mg/m². Program discontinued (Phase 2 terminated) for insufficient efficacy + ocular toxicity. CTCAE version not stated in sources (study era ~2006-2009 = CTCAE v3.0 era). DM4 payload physchem (MW 780.4, xLogP3 3.2, logD 3.0, TPSA 157, pKa 10.3, neutral, bystander Yes) and SPDB linker physchem (LIN0VZYER; same SPDB as coltuximab ravtansine) reused from class-standard values; SPDB is the non-sulfonated disulfide (no sulfonate masking; mirvetuximab uses sulfo-SPDB). dar_mean 3.5 = midpoint of ADCdb/ADC Review 'DAR 3-4'. Trials per screen: NCT00352131, NCT00620607. Note interim AACR abstract reported n=36 treated; the final Ph1 publication and Eaton 2015 review report n=30 (used here). Confidence: composition/chemistry/payload from ADCdb + secondary sources (C); dosing/MTD and Ph1 ocular DLT pattern peer-reviewed (B); RP2D 50% ocular rate from Ph2 ASCO 2009 abstract corroborated by Eaton 2015 review (D-to-C).