ADC TOXICITY ATLAS
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Sacituzumab tirumotecan

Approved (ex-US)
sac-TMT; SKB264; SKB-264; MK-2870; MK2870; A-264; KL-A264; Jiatailai
Sponsor
Sichuan Kelun-Biotech (KLUS Pharma); Merck & Co. (ex-China rights)
Indication
TROP2+ metastatic triple-negative breast cancer (2L+); EGFR-mutant NSCLC
Target family
TACSTD / EpCAM-TROP
RP2D dose
5 mg/kg
Q2W (every 2 weeks)RP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
2.3%
G3+
0%
RP2D
sagittal schematic · Unknown

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
65.43%
Limbus
AE
-
Express.
73.31%
Conjunctiva
AE
-
Express.
86.39%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
0%
0 nTPM
Dominant tissue
Ocular surface
Surface subtype
Mixed
Reversibility
Unknown
Reported ocular events
Ocular surface toxicity (composite ocular-surface term)9.6%
n=188
Xerophthalmia (dry eye)2.3%
G3+ 0%n=130
Vision blurred1%
G3+ 0%n=91
Ophthalmodynia (eye pain)1%
n=91
Ocular surface toxicity-
G3+ 0%n=188
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
7.4
DAR
Payload
Topoisomerase I inhibitor (belotecan-derived camptothecin); arrests cell cycle at G2/S
Linker structureC47H72N10O14
NCCCCC(NC(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCn1cc(NC(=O)CCCC#Cc2cncnc2)nn1)C(=O)Nc1ccc(CO)cc1
Payload structureC26H29N3O6S
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CCN(C(C)C)S(=O)(=O)C)O
03
Antibody

Antibody & Fc engineering

Antibody
Sacituzumab (hRS7; same amino-acid sequence as IMMU-132/sacituzumab govitecan)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None (wild-type IgG1 Fc; no silencing mutations)
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Sulfonyl pyrimidine-CL2A-carbonate (ADCdb: Pyrimidine-CL2A-carbonate)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys (TCEP-reduced interchain disulfides; sulfonyl-pyrimidine NAS)
Symmetry
Symmetric
DAR (mean)
7.4
DAR homogeneity
Heterogeneous
Plasma t½
2.3 d
Cleavage trigger
pH/acid (benzyl-carbonate hydrolysis); non-enzymatic
Release control
Conditional
Hydrophilicity mask
Discrete-PEG-spacer
Formula
C47H72N10O14
Linker MW
1001.149 Da
Linker TPSA
302.21 Ų
Linker xLogP
0.239
ADCdb linker
LIN0ZEYRW
In-vitro stability
~70% payload released @144h / human plasma (in vivo payload t1/2 56.3 h vs IMMU-132 15.5 h)
05
Payload

Payload & physicochemistry

Payload profile
Payload
KL610023 (also T030; belotecan-derived)
Class
Topoisomerase I inhibitor
Mechanism
Topoisomerase I inhibitor (belotecan-derived camptothecin); arrests cell cycle at G2/S
Released catabolite
KL610023 (free belotecan-derived TOP1 inhibitor; rapidly eliminated, t1/2 ~1.6 h in cynomolgus)
Mechanistic subtype
TopoI
Stereochem / salt
No salt/counterion specified for the ADC drug substance; KL610023 is a belotecan-derived (20S) camptothecin-class payload
Bystander
Yes
PAMPA rank
-
MW
511.6 Da
XLogP3
1.3
logD₇.₄
-
TPSA
125 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
1
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C26H29N3O6S
PubChem CID
139294971
ADCdb payload
PAY0BBRSF
Bioactivity note
ADCdb cell-line IC50 (ADC): Calu-3 1.28 nM, NCI-N87 2.24 nM, NCI-H23 3.41 nM, HCC1806 5.7 nM, BxPC-3 11.03 nM; in vivo tumor growth inhibition ~39-100% across PDX/xenografts depending on dose and TROP2 expression. Free payload KL610023 cytotoxic potency ~1.5x greater than SN-38 (
06
Dosing & regimen

Dosing

RP2D dose
5 mg/kg
Schedule
Q2W (every 2 weeks)
Route
IV
Fractionated
No
n at RP2D
130
Dose basis
TBW
Trial phase
Approved
Dose-OAE available
No
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
2.3 %
OAE grade 3+
0 %
OAE data status
reported
Severity (weighted)
0.69
Keratopathy
-
Conjunctival
-
Dry eye
2.3 %
Blurred vision
1.5 %
Dominant tissue
Ocular surface
Surface subtype
Mixed
Grading scale
CTCAE v5
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
65.43 %
Cornea (limbal)
73.31 %
Conjunctiva
86.39 %
RPE
0 %
Retina (HPA)
0 nTPM
Cross-trial comparability
Ascertainment: Partial / unspecified monitoringScale: CTCAE v5Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
sacituzumab-tirumotecan
Approval status
Approved (ex-US)
Approval year
2024
UniProt
P09758
ADCdb ADC
DRG0BSQPI
ADCdb antibody
ANI0INHAA
ADCdb target
PATR0EGDKN
Primary source
OptiTROP-Breast01 Ph3 (Nat Med 2025, s41591-025-03630-w); ocular rates per Frontiers 2026 ADC ocular-tox review (fimmu.2026.1698458)
Aliases & development codes
sac-TMT; SKB264; SKB-264; MK-2870; MK2870; A-264; KL-A264; Jiatailai
Notes
CORRECTION to screen/ADCdb: ADCdb lists "Approved (FDA): Nov 2024", but this is actually China NMPA approval (Kelun-Biotech, 2024-11-27, 2L+ mTNBC; NSCLC added 2025). Sac-TMT is NOT FDA-approved; FDA granted only Breakthrough Therapy Designation (Dec 2024, EGFRm NSCLC). Recorded approval_status as "Approved (China NMPA)". ANTIBODY: Sac-TMT shares the SAME anti-TROP2 antibody (sacituzumab/hRS7, humanized IgG1, identical sequence to IMMU-132) as sacituzumab govitecan already in the DB, but differs in payload (KL610023, a belotecan-derived TOP1 inhibitor vs SN-38) and linker (sulfonyl pyrimidine-CL2A-carbonate vs CL2A maleimide). DAR 7.4 (ADCdb "7 to 8"). Useful as a low-OAE TROP2 ADC comparator. OCULAR (priority): Fully cross-verified by the dedicated Frontiers 2026 ADC ocular-toxicity review (fimmu.2026.1698458): OptiTROP-Breast01 (N=130, 5 mg/kg Q2W) xerophthalmia 2.3% (all G1-2), blurred vision 1.5% (all G1), no grade >=3; OptiTROP-Lung03 Part II (N=91) blurred vision + ophthalmodynia each ~1% (G1); KL264-01 one dry-eye case led to discontinuation among ~36 TNBC pts. oae_any_pct=2.3 = max PT (xerophthalmia) at RP2D. ocular_surface_subtype="Mixed" (dry eye = ocular surface + blurred vision = visual; no keratopathy/conjunctivitis). PAYLOAD PHYSCHEM: KL610023 (T030) is not in PubChem by name; no KL610023-specific MW/XLogP3/logD/TPSA/pKa/charge retrievable from PubChem or the chemistry literature, so those cells left blank (conservative). Bystander effect = Yes (well documented, PMC9817100). Parent belotecan (PubChem CID 6456014: C25H27N3O4, MW 433.5, XLogP 1.6, TPSA 91.8) noted for context only; NOT substituted because KL610023 is a distinct derivative. DOSING: 5 mg/kg IV Q2W (single infusion per cycle, not fractionated). The PMC review's "4 mg/kg" appears to be an extraction error; 5 mg/kg Q2W is corroborated by the ASCO abstract, Nature Medicine paper, and Frontiers ocular review. TOXICITY caveats: Any-grade TRAEs are from the Nat Med 2025 / ASCO 2024 OptiTROP-Breast01 table (n=130, RP2D). Headline grade >=3 TRAEs: neutrophil 32.3%, anaemia 27.7%, WBC 25.4% (overall grade >=3 TRAE 57.7%). Breast01-specific grade >=3 values for thrombocytopenia/stomatitis/ALT/AST were not separately retrieved (left to any-grade rows). Pulmonary ILD and peripheral neuropathy rows entered as pct=0 (tier C) based on reported-absence statements (KL264-01/review), not Breast01 tabulations - both notable negatives for a TOP1 ADC. Rash (31%) and alopecia omitted (no matching organ_system enum). No infusion-reaction data retrieved (Infusion left blank). Linker_plasma_t_half=2.3 d derived from preclinical in vivo payload t1/2 56.3 h (PMC9817100; vs IMMU-132 15.5 h) - methodologically comparable to how govitecan's 0.7 was derived.