ADC TOXICITY ATLAS
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Praluzatamab ravtansine

Investigational
CX-2009; Probody-drug conjugate
Sponsor
CytomX
Indication
ALCAM+ solid tumors
Target family
Nectin / Ig-CAM
RP2D dose
7 mg/kg (Q3W MTD/RP2D)
Q2W or Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
11 adverse-event terms

Ocular

Any-grade
49%
G3+
11%
RP2D
sagittal schematic · Reversible
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
9%
Express.
5.87%
Limbus
AE
-
Express.
13.48%
Conjunctiva
AE
-
Express.
59.71%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
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
Keratopathy3.03%
non-seriousn=99
Eye pain3.03%
non-seriousn=99
Photophobia3.03%
non-seriousn=99
Punctate keratitis3%
n=99
Conjunctivitis2.02%
non-seriousn=99
Cellulitis orbital-
Corneal infiltrates-
Per-trial detail

Adverse events by trial

PROCLAIM-CX-2009 (NCT03149549) — all cohorts pooled (all-cause any-grade)Phase 1/20.25-10 mg/kg (all dose levels) Q3W or Q2Wn=99CTCAE CTCAE v4.03 (MedDRA 16PooledCto verify
CT.gov NCT03149549 (PROCLAIM-CX-2009) posted results, adverseEventsModule (pooled across dose arms) NCT03149549 (pooled)
199 adverse-event terms · 22 systems · expand a system below
GI22
Nausea
46.5%
46/99
Diarrhoea
28.3%
28/99
Vomiting
24.2%
24/99
Constipation
22.2%
22/99
Abdominal pain
16.2%
16/99
Dyspepsia
8.1%
8/99
Ascites
6.1%
6/99
Dry mouth
6.1%
6/99
Abdominal distension
5.1%
5/99
Abdominal pain upper
3%
3/99
Abdominal discomfort
2%
2/99
Abdominal pain lower
2%
2/99
Gastritis
2%
2/99
Aphthous ulcer
1%
1/99
Flatulence
1%
1/99
Gastrooesophageal reflux disease
1%
1/99
Gingival bleeding
1%
1/99
Odynophagia
1%
1/99
Proctalgia
1%
1/99
Small intestinal obstruction
1%
1/99
Toothache
1%
1/99
Upper gastrointestinal haemorrhage
1%
1/99
Pulmonary19
Ocular18
Keratitis
23.2%
23/99
Vision blurred
19.2%
19/99
Dry eye
10.1%
10/99
Eye pain
3%
3/99
Keratopathy
3%
3/99
Photophobia
3%
3/99
Punctate keratitis
3%
3/99
Asthenopia
1%
1/99
Astigmatism
1%
1/99
Cataract
1%
1/99
Chalazion
1%
1/99
Corneal infiltrates
1%
1/99
Eyelid ptosis
1%
1/99
Orbital cyst
1%
1/99
Presbyopia
1%
1/99
Pupillary reflex impaired
1%
1/99
Retinal degeneration
1%
1/99
Visual impairment
1%
1/99
General17
Investigations16
Metabolic16
Neurologic (other)15
Dermatologic13
Musculoskeletal12
Infections11
Renal7
Other5
Vascular5
Hematologic4
Injury4
Psychiatric4
Endocrine3
Cardiac2
Ear2
Neoplasms2
Hepatic1
Immune1
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
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
03
Antibody

Antibody & Fc engineering

Antibody
CX-191 Probody (praluzatamab)
Isotype
IgG1
Origin
Humanized
Fc modifications
None reported; Probody protease-cleavable mask on the light chain (Fc not characterised in the cited source)
Glycoengineering
Standardinferred
Effector silencing
Noneinferred
FcγR binding
Retained
C1q binding
Retainedinferred
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
SPDB
Class
Cleavable
Cleavage
Cleavable
Attachment
Lysine
Conjugation
Conventional Lys (SPDB)
Symmetry
Asymmetric
DAR (mean)
3.5
DAR homogeneity
Heterogeneous
Plasma t½
5.24 d
Cleavage trigger
GSH/reductive (disulfide)
Release control
Conditional
Hydrophilicity mask
Noneinferred
Platform
Probody drug conjugateunver.
Formula
C13H14N2O4S2
Linker MW
326.399 Da
Linker TPSA
127.17 Ų
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)
05
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
-
MW
780.4 Daconflicts
XLogP3
3.2
logD₇.₄
3
TPSA
157 Ų
pKa
10.3 pKa
Charge pH 7.4
0
H-bond donors
3
H-bond acceptors
11
IC50 (HCEC)
-
Formula
C39H56ClN3O10S
PubChem CID
46926355
ADCdb payload
PAY0GTSVM
Hydrophobicity · logD₇.₄
hydrophilic −2+3+4 lipophilic
06
Dosing & regimen

Dosing

RP2D dose
7 mg/kg (Q3W MTD/RP2D)
Schedule
Q2W or Q3W
Route
IV
Fractionated
No
n at RP2D
99basis?
Dose basis
TBW
Trial phase
Phase 1/2
Dose-OAE available
Yes
Tox summary basis
RP2D
Conditional activation
Peptide CDR mask cleaved by tumor-associated proteases
08
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 %unver.
Conjunctival
-
Dry eye
-
Blurred vision
16 %unver.
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)
5.87 %
Cornea (limbal)
13.48 %
Conjunctiva
59.71 %
RPE
-
Retina (HPA)
3.3 nTPM
Cross-trial comparability · source-verified
Ascertainment: Partial / unspecified monitoringScale: CTCAE v4Denominator: RP2D
Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort
4 mg/kg
Q2W
50%
n=4 · PROCLAIM-CX-2009
4 mg/kg
Q2W
25%
n=4 · PROCLAIM-CX-2009
4 mg/kg
Q3W
10%
n=10 · PROCLAIM-CX-2009
0.25-4 mg/kg
Q3W
10%
n=20 · PROCLAIM-CX-2009
5 mg/kg
Q3W
66.7%
n=9 · PROCLAIM-CX-2009
5 mg/kg
Q3W
22.2%
n=9 · PROCLAIM-CX-2009
5 mg/kg
Q3W
11.1%
n=9 · PROCLAIM-CX-2009
5 mg/kg
3%
n=99
6 mg/kg
Q2W
83.3%
n=6 · PROCLAIM-CX-2009
6 mg/kg
Q3W
33.3%
n=9 · PROCLAIM-CX-2009
6 mg/kg
Q2W
33.3%
n=6 · PROCLAIM-CX-2009
6 mg/kg
Q3W
22.2%
n=9 · PROCLAIM-CX-2009
6 mg/kg
Q2W
16.7%
n=6 · PROCLAIM-CX-2009
6 mg/kg
Q3W
11.1%
n=9 · PROCLAIM-CX-2009
7 mg/kg
Q3W
25%
n=12 · PROCLAIM-CX-2009
Pooled all doses (RP2D 7 mg/kg Q3W)
Q3W + Q2W (pooled)
23.2%
n=99 · PROCLAIM-CX-2009
7 mg/kg
Q3W
8.3%
n=12 · PROCLAIM-CX-2009
8 mg/kg
Q3W
54.5%
n=22 · PROCLAIM-CX-2009
8 mg/kg
Q3W
9.1%
n=22 · PROCLAIM-CX-2009
8 mg/kg
Q3W
4.5%
n=22 · PROCLAIM-CX-2009
9 mg/kg
Q3W
55.6%
n=9 · PROCLAIM-CX-2009
9 mg/kg
Q3W
22.2%
n=9 · PROCLAIM-CX-2009
9 mg/kg
Q3W
22.2%
n=9 · PROCLAIM-CX-2009
10 mg/kg
Q3W
75%
n=8 · PROCLAIM-CX-2009
10 mg/kg
Q3W
50%
n=8 · PROCLAIM-CX-2009
0.25-10 mg/kg (all dose levels)
Q3W or Q2W
43.4%
n=99 · PROCLAIM-CX-2009
10 mg/kg
Q3W
12.5%
n=8 · PROCLAIM-CX-2009
0.25-10 mg/kg (all dose levels)
Q3W or Q2W
9.1%
n=99 · PROCLAIM-CX-2009
0.25-10 mg/kg (all dose levels)
Q3W or Q2W
1%
n=99 · PROCLAIM-CX-2009
—
23.23%
n=99 · PROCLAIM-CX-2009: A Trial to Find Safe and Active Doses of an Investigational Dr
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
09
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)no such source
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.no such source