Praluzatamab ravtansine

Investigational

CX-2009; Probody-drug conjugate

Target

ALCAM (CD166) · ALCAM

Sponsor

CytomX

Indication

ALCAM+ solid tumors

Target family

Nectin / Ig-CAM

RP2D dose

7 mg/kg (Q3W MTD/RP2D)

Q2W or Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

10 adverse-event terms

Ocular

Any-grade

49%

G3+

11%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

5.87%

Limbus

Express.

13.48%

Conjunctiva

Express.

59.71%

Lens

Express.

Retina / RPE

Express.

3.3 nTPM

Off-target signature

9% corneal toxicity, yet the ALCAM (CD166) target is detected in only 5.87% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular toxicity (composite)43%

G3+ 11%n=99

Keratitis23.2%

G3+ 9%n=99

Vision blurred19.2%

n=99

Dry eye10.1%

n=99

Punctate keratitis3%

Keratopathy-

Eye pain-

Photophobia-

Cellulitis orbital-

Corneal infiltrates-

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

3.5

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 structureC39H56ClN3O10S

CC1=CC=CC(C2(CC(C(C3C(O3)(C(CC(=O)N(C4=C(C(=CC(=C4)C1)OC)Cl)C)OC(=O)C(C)N(C)C(=O)CCC(C)(C)S)C)(C)C)OC(=O)N2)O)OC

Antibody

Antibody & Fc engineering

Antibody

CX-191 Probody (praluzatamab)

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 (SPDB)

Symmetry

Asymmetric

DAR (mean)

3.5

DAR homogeneity

Heterogeneous

Plasma t½

5.5 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

Inherited from SPDB-DM4 class; Boni CCR 2022 PROCLAIM Ph1/2 reports "CX-2009 circulates predominantly intact at all doses; PK not strongly influenced by target-mediated drug disposition" but does not give numeric t½ in d in the open figure captions; Probody mask cleavable in tumor microenvironment by proteases (does not affect plasma stability of intact ADC)

Payload

Payload & physicochemistry

Payload profile

Payload

DM4 (free)

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (DM4-Me)

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

C39H56ClN3O10S

PubChem CID

46926355

ADCdb payload

PAY0GTSVM

Hydrophobicity · logD₇.₄

hydrophilic −2+3+4 lipophilic

Dosing & regimen

Dosing

RP2D dose

7 mg/kg (Q3W MTD/RP2D)

Schedule

Q2W or Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1/2

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

49 %

OAE grade 3+

11 %

OAE data status

reported

Severity (weighted)

22.4

Keratopathy

9 %

Conjunctival

Dry eye

Blurred vision

16 %

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)

5.87 %

Cornea (limbal)

13.48 %

Conjunctiva

59.71 %

RPE

Retina (HPA)

3.3 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

praluzatamab-ravtansine

Approval status

Investigational

Approval year

UniProt

Q13740

ADCdb ADC

DRG0QTTWI

ADCdb antibody

ANI0SPXDP

ADCdb target

TAR0UPRHI

Primary source

Boni CCR 2022 (PROCLAIM-CX-2009)

Aliases & development codes

CX-2009; Probody-drug conjugate

Notes

Strong dose-dependence across 7 dose levels Q3W + 2 Q2W cohorts. V3.1: RP2D corrected 4→7 mg/kg Q3W per Boni 2022 (4 mg/kg was a lower dose level). OAE 43→49%. Keratitis 21→9% (prev 21 may have pooled multiple corneal terms). PMID corrected 35046062→35165101.