ADC TOXICITY ATLAS
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ZV0203

Investigational
Sponsor
Zhejiang Hisun Pharmaceutical; Zhejiang Zova Biotherapeutics
Indication
HER2-positive advanced solid tumors (phase 1: breast, colorectal, gastric, lung; phase 2a: esophageal, colorectal, prostate)
Target family
Receptor tyrosine kinase
RP2D dose
-
Q3W (every 21 days)Pooled
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
60%
G3+
26.7%
Pooled
sagittal schematic · Reversible

Tissues shaded by reported adverse-event rate.

Cornea
AE
60%
Express.
46.2%
Limbus
AE
-
Express.
61.99%
Conjunctiva
AE
-
Express.
61.13%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
5.48%
7.5 nTPM
Off-target signature

60% corneal toxicity, yet the Receptor tyrosine-protein kinase erbB-2 (HER2) target is detected in only 46.2% of central cornea - toxicity is not explained by target expression.

Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Reversibility
Reversible
Reported ocular events
Corneal epitheliopathy60%
G3+ 6.7%n=15
Dry eye40%
n=15
Blurred vision-
G3+ 20%n=15
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
2
DAR
Payload
Microtubule/tubulin polymerization inhibitor (antimitotic)
Linker structureC21H36N6O7
CC(C)[C@H](NC(=O)CCC(=O)N1CCC(C(N)=O)CC1)C(=O)N[C@@H](CCCNC(N)=O)C(=O)O
Payload structureC40H69N9O6
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=C(C=C2)N)CN=[N+]=[N-])OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
03
Antibody

Antibody & Fc engineering

Antibody
Pertuzumab
Isotype
IgG1
Origin
Humanized
Fc modifications
-
Glycoengineering
-
Effector silencing
-
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Pip-Val-Cit
Class
Peptide
Cleavage
Cleavable
Attachment
-
Conjugation
-
Symmetry
-
DAR (mean)
2
DAR homogeneity
-
Plasma t½
-
Cleavage trigger
Cathepsin B (lysosomal cysteine protease); Val-Cit dipeptide
Release control
Conditional
Hydrophilicity mask
None
Formula
C21H36N6O7
Linker MW
484.554 Da
Linker TPSA
214.02 Ų
Linker xLogP
-1.3508
ADCdb linker
LIN0FCZJP
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
Duostatin 5 (Duo-5/DUO5)
Class
Auristatin
Mechanism
Microtubule/tubulin polymerization inhibitor (antimitotic)
Released catabolite
Duostatin 5 (auristatin payload)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
-
PAMPA rank
-
MW
772 Da
XLogP3
5.5
logD₇.₄
-
TPSA
161 Ų
pKa
-
Charge pH 7.4
+1
H-bond donors
3
H-bond acceptors
10
IC50 (HCEC)
-
Formula
C40H69N9O6
PubChem CID
138320017
ADCdb payload
PAY0EQOWS
06
Dosing & regimen

Dosing

RP2D dose
-
Schedule
Q3W (every 21 days)
Route
IV
Fractionated
No
n at RP2D
-
Dose basis
-
Trial phase
Phase 1/2
Dose-OAE available
Yes
Tox summary basis
dose-escalation
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
60 %
OAE grade 3+
26.7 %
OAE data status
reported
Severity (weighted)
36.69
Keratopathy
60 %
Conjunctival
-
Dry eye
40 %
Blurred vision
20 %
Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Grading scale
CTCAE (unversioned)
Reversibility
Reversible
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
46.2 %
Cornea (limbal)
61.99 %
Conjunctiva
61.13 %
RPE
5.48 %
Retina (HPA)
7.5 nTPM
Cross-trial comparability
Ascertainment: Monitoring unknownScale: CTCAE (unversioned)Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
zv0203
Approval status
Investigational
Approval year
-
UniProt
P04626
ADCdb ADC
DRG0NMCNK
ADCdb antibody
ANI0XJJLY
ADCdb target
TAR0THKZD
Primary source
ESMO 2024 abstr 335P (Ann Oncol S0923-7534(24)01793-9); ASCO 2024 JCO 42(16_suppl):e15004; ESMO 2023 abstr 438P (Ann Oncol S0923-7534(23)01450-3); ADCdb DRG0NMCNK; PubChem CID 138320017; NCT05423977
Notes
ZV0203 = pertuzumab-Pip-Val-Cit-Duostatin 5 ADC (HER2/ERBB2, DAR 2, Zhejiang Hisun/Zova). First-in-human phase 1/2a NCT05423977; phase 1 dose escalation 0.3-3.6 mg/kg IV Q3W (N=15, 3+3); phase 2a at 4.3 and 5.0 mg/kg. No DLTs, MTD not reached, formal RP2D not declared in available abstracts. DATA CUTS: Two readouts exist. (1) ESMO 2023 438P (cut Aug 23, 2023): TRAE 11/15 (73.3%); corneal epitheliopathy 5, dry eye 4, elevated liver enzymes 6, leukopenia/neutropenia/proteinuria/anaemia 3 each. (2) Mature cut Jan 18, 2024 (ASCO 2024 e15004 / ESMO 2024 335P): TRAE 14/15 (93.3%); corneal epitheliopathy 9/15 (60%, MOST COMMON TRAE), dry eye 6/15 (40%), elevated liver enzymes 6/15 (40%), neutropenia 4/15, anaemia 4/15, leukopenia 3/15, proteinuria 3/15. Headline figures use the mature cut, which matches the curator's oae_hint (corneal 60%, dry eye 40%); the input hint is CONFIRMED CORRECT (an earlier search of the Aug-2023 cut had transiently suggested corneal 5/15, but the later cut supersedes it). OCULAR: Corneal epitheliopathy is the dominant/characteristic finding (classic off-target auristatin keratopathy), plus dry eye and blurred vision -> ocular_surface_subtype 'Corneal (off-target)'. oae_any_pct=60 (corneal, max ocular PT). Grade 3 ocular: corneal epitheliopathy 1/15 (6.7%, at 3.6 mg/kg) + blurred vision 3/15 (20%, 2 at 2.7 + 1 at 3.6 mg/kg). oae_g3plus_pct reported as the max single G3 ocular PT (blurred vision 20%); total distinct G3-ocular patients <=4/15 (26.7%) but a patient at 3.6 mg/kg may have both events (possible overlap), so 20% is the conservative value. 2/15 (13.3%) discontinued due to TRAEs. NOT CAPTURED IN ROWS: proteinuria 3/15 (20%, renal) — renal is outside the organ_system enum, recorded here only. PAYLOAD CAVEAT: PubChem 'Duostatin 5' (CID 138320017, C40H69N9O6, MW 772.0, xLogP3 5.5, TPSA 161, formal charge 0) carries an aminophenyl + azidomethyl terminus (likely a synthetic/conjugation handle) and lacks the free C-terminal carboxylate of parent MMAF; logD7.4 and pKa are not PubChem-computed. payload_charge_pH7_4 (+1) and bystander status are estimates/uncertain. ISOTYPE: ADCdb lists antibody isotype 'not disclosed' for the ADC; humanized IgG1-kappa is inferred from the pertuzumab backbone. DEDUPE FLAG (from input): a near-duplicate-looking entry 'anti-HER2-vc-Duostatin-5 site-specific' may exist in known_names but appears to be a generic/preclinical anti-HER2 research construct, NOT this specific pertuzumab-based clinical ADC — keep separate / verify before merging. CONFIDENCE: All clinical/dosing/ocular/toxicity data are conference-abstract level (tier D); no full peer-reviewed primary publication located. Composition/linker (ADCdb) and payload physchem (PubChem computed) are tier C.