ADC TOXICITY ATLAS
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Trastuzumab rezetecan

Approved (ex-US)
SHR-A1811; SHR A1811; SHRA1811; Aiweida; Avida
Sponsor
Jiangsu Hengrui Pharmaceuticals (Suzhou Suncadia Biopharmaceuticals; ex-China: Luzsana Biotechnology)
Indication
HER2-mutant advanced/metastatic NSCLC (>=2L)
Target family
Receptor tyrosine kinase
RP2D dose
4.8 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
3.3%
G3+
3.3%
RP2D
sagittal schematic · -

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
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
Dominant tissue
Ocular surface
Surface subtype
Mixed
Reversibility
-
Reported ocular events
Ulcerative keratitis-
G3+ 3.3%n=1
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
5.7
DAR
Payload
TopoI inhibitor
Linker structureC25H31N5O8
[H]OC(=O)C([H])([H])N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])N([H])C(=O)C([H])([H])N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(=O)C([H])=C([H])C1=O)C([H])([H])c1c([H])c([H])c([H])c([H])c1[H]
Payload structureC29H28FN3O6
CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)NC(=O)C(C7CC7)O)O
03
Antibody

Antibody & Fc engineering

Antibody
trastuzumab
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Mc-Gly-Gly-Phe-Gly (GGFG tetrapeptide)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys (maleimide)
Symmetry
Symmetric
DAR (mean)
5.7
DAR homogeneity
Heterogeneous
Plasma t½
-
Cleavage trigger
Cathepsin B/L (GGFG tetrapeptide)
Release control
Conditional
Hydrophilicity mask
Hydrophilic-linker
Formula
C25H31N5O8
Linker MW
529.55 Da
Linker TPSA
191.08 Ų
Linker xLogP
-1.3675
ADCdb linker
LIN0ECMCR
In-vitro stability
>98%@21d/human-plasma
05
Payload

Payload & physicochemistry

Payload profile
Payload
Rezetecan (SHR9265 / SHR169265)
Class
Topoisomerase I inhibitor
Mechanism
TopoI inhibitor
Released catabolite
Rezetecan (SHR169265) - the free TopoI-inhibitor payload (exatecan derivative) released after cathepsin B/L cleavage of the GGFG linker
Mechanistic subtype
TopoI
Stereochem / salt
Payload SHR169265 is a single defined stereoisomer (exatecan derivative with a chiral cyclopropyl at the carbonyl alpha-position); conjugate salt form not specified in accessible sources
Bystander
Yes
PAMPA rank
-
MW
533.55 Da
XLogP3
3.67
logD₇.₄
1.89
TPSA
129 Ų
pKa
-
Charge pH 7.4
+1
H-bond donors
3
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C29H28FN3O6
PubChem CID
172874939
ADCdb payload
PAY0CJNCU
Hydrophobicity · logD₇.₄
hydrophilic −2+1.89+4 lipophilic
Bioactivity note
Payload SHR9265/SHR169265 is a DNA topoisomerase I (TOP1) inhibitor (exatecan-derived camptothecin; TOP1 inhibition comparable to SHR167971/DXd-class). ADC SHR-A1811 (DAR ~6) cytotoxicity IC50 0.3-2.32 nM across nine cancer cell lines; bystander killing IC50 0.23 +/- 0.05 nM on H
06
Dosing & regimen

Dosing

RP2D dose
4.8 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
94
Dose basis
TBW
Trial phase
Phase 2
Dose-OAE available
Partial
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
-
OAE grade 3+
3.3 %
OAE data status
reported
Severity (weighted)
-
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
Ocular surface
Surface subtype
Mixed
Grading scale
CTCAE v5
Reversibility
-
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 · source-verified
Ascertainment: Symptom-driven reportingScale: CTCAE v5Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
trastuzumab-rezetecan
Approval status
Approved (ex-US)
Approval year
2025
UniProt
P04626
ADCdb ADC
DRG0CECRA
ADCdb antibody
ANI0FIZAK
ADCdb target
TAR0THKZD
Primary source
HORIZON-Lung Ph2 (Lancet Oncol 2025, PIIS1470-2045(25)00012-9); HORIZON-X global Ph1 (JCO 2024, JCO.23.02044, NCT04446260); SHR-A1811 NSCLC Ph1/2 (Nat STTT 2024, PMC11247081); China NMPA Aiweida label (pooled 3-trial); Frontiers 2026 ADC ocular review (10.3389/fimmu.2026.1698458); ADCdb DRG0CECRA; PLOS One 2025 (PMC12200682)
Aliases & development codes
SHR-A1811; SHR A1811; SHRA1811; Aiweida; Avida
Notes
SHR-A1811 = trastuzumab rezetecan (Aiweida/Avida), China's first domestically developed ADC; NMPA-approved 2025-05-29 for HER2-mutant advanced/metastatic NSCLC (>=2L), basis HORIZON-Lung. Sponsor Jiangsu Hengrui (ex-China: Luzsana). Composition: trastuzumab (humanized IgG1-kappa, anti-HER2) + Mc-GGFG cleavable tetrapeptide linker = LIN0ECMCR, structurally IDENTICAL to the deruxtecan linker shared with T-DXd and Dato-DXd in the DB (linker physchem carried from that shared ADCdb/PubChem entry: C25H31N5O8, MW 529.55, TPSA 191.08, xLogP -1.3675) + rezetecan (SHR9265/SHR169265), a DISTINCT exatecan-derived TopoI inhibitor (chiral cyclopropyl at the carbonyl alpha-position; MW 533.55; LogD7.4 1.89; ALogP 3.67; membrane Peff ~5x DXd; bystander-positive) -- so payload values were taken from the SHR-A1811 characterization paper, NOT copied from DXd. DAR ~5.7 (ADCdb measured range 5.3-6.4; design-nominal ~6). In-vitro stability <2% payload release at 21 d in human plasma (>98% retained). OCULAR (the qualifying signal, kept conservative): China NMPA pooled 3-trial label lists blurred vision as 'common' (CIOMS band ~1-10%; no published point estimate) with conjunctival hyperaemia and lacrimation increased 'infrequent' (~0.1-1%); global Ph1 HORIZON-X reported 1 grade-3 ulcerative keratitis among 30 non-Asian pts at 4.8 mg/kg (3.3%). The NSCLC Ph1/2 (N=63) and pivotal HORIZON-Lung (N=94) AE tables listed NO ocular AEs, so blurred vision is recorded only qualitatively in the ocular group (band, not a fabricated numeric row); the single numeric ocular toxicity row is the G3 keratitis. Frontiers 2026 review notes no reversibility data and no post-marketing ocular reports for this drug. TOXICITY pattern is hematologic-dominant: pivotal HORIZON-Lung (N=94, 4.8 mg/kg, CTCAE v5.0) G3+ -> neutropenia 40%, WBC decreased 27%, anaemia 23%, thrombocytopenia 11%, lymphopenia 7% (overall G3+ TRAE 62%); the any-grade panel is from the same NSCLC program reported earlier as Ph1/2 (N=63, CTCAE v5.0) -> neutropenia 79.4%, anaemia 76.2%, WBC 73.0%, platelets 42.9%, nausea 79.4%, vomiting 60.3%, decreased appetite 55.6%, fatigue/asthenia 60.3%, alopecia 41.3%, ALT 42.9%, AST 39.7%, bilirubin 14.3% (hepatic transaminitis all low-grade, 0 G3+). ILD is the key class risk: ~11.6% (5/43) low-grade at RP2D, 11.1% (7/63) whole NSCLC cohort including 1 G5 fatal in the higher 6.4 mg/kg cohort (no fatal ILD at RP2D), vs 2.5% across all tumors in global Ph1 (N=307). Peripheral neuropathy and infusion-related reactions were not reported (consistent with the DXd/TopoI class) -> left blank. Caveats recorded in cells: payload charge +1 is inferred (tier C) from the conserved exatecan primary amine; payload TPSA/pKa left blank (not measured for SHR169265); the payload_xlogp3 cell holds the paper's ALogP (3.67), not a PubChem XLogP3. Fatigue/asthenia and alopecia are documented but omitted from toxicity_rows because they fall outside the fixed organ_system enum. CTCAE v5.0 throughout. Note ADCdb labels approval as 'FDA Approval May 2025' but the actual regulatory action was China NMPA (2025-05-29); recorded as NMPA-approved.