ADC TOXICITY ATLAS
AtlasPayloads and LinkersPayloadsTargetsQueryMethods
← Atlas

Sacituzumab govitecan

FDA-approved
Trodelvy; IMMU-132
Sponsor
Immunomedics/Gilead
Indication
TACSTD2+ TNBC / urothelial
Target family
TACSTD / EpCAM-TROP
RP2D dose
10 mg/kg
D1+D8 Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
5%
G3+
0%
RP2D
sagittal schematic · Reversible
↳

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
-
Surface subtype
Anterior ocular-surface / lacrimal
Reversibility
Reversible
Reported ocular events
No granular adverse-event rows recorded for this system.
Per-trial detail

Adverse events by trial

IMMU-132-01 (NCT01631552)Phase 1/210 mg/kg IV Days 1 and 8 of 21-day cycle (doses up to 10 mg/kg)n=495CTCAE 4.0B
ClinicalTrials.gov posted results — NCT01631552 (Serious AE) NCT01631552
84 adverse-event terms · 20 systems · expand a system below
Infections19
Clostridium difficile infection
0.2%
1/495
Covid-19 pneumonia
0.2%
1/495
Diverticulitis
0.2%
1/495
Enterocolitis infectious
0.2%
1/495
Epiglottitis
0.2%
1/495
Escherichia infection
0.2%
1/495
Escherichia urinary tract infection
0.2%
1/495
Herpes zoster
0.2%
1/495
Influenza
0.2%
1/495
Liver abscess
0.2%
1/495
Peritonitis
0.2%
1/495
Pleural infection
0.2%
1/495
Pyelonephritis
0.2%
1/495
Rectal abscess
0.2%
1/495
Respiratory syncytial virus infection
0.2%
1/495
Septic shock
0.2%
1/495
Staphylococcal bacteraemia
0.2%
1/495
Upper respiratory tract infection
0.2%
1/495
Vascular device infection
0.2%
1/495
Pulmonary11
GI8
Injury8
General4
Metabolic4
Neoplasms4
Neurologic (other)4
Hematologic3
Cardiac3
Hepatic3
Musculoskeletal2
Psychiatric2
Renal2
Vascular2
Endocrine1
Ocular1
Purtscher retinopathy
0.2%
1/495
Immune1
Other1
Dermatologic1
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
Cleavable
7.6
DAR
Payload
SN-38
TopoI inhibitor
Linker structureC50H79N9O16
[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])OC([H])([H])C(=O)N([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])n2nnc(C([H])([H])N([H])C(=O)C3([H])C([H])([H])C([H])([H])C([H])(C([H])([H])N4C(=O)C([H])=C([H])C4=O)C([H])([H])C3([H])[H])c2[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])c([H])c1[H]
Payload structureC22H20N2O5
CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)[C@@]4(CC)O)C2=NC5=C1C=C(C=C5)O
03
Antibody

Antibody & Fc engineering

Antibody
hRS7 (sacituzumab)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
Target KD (nM)
1.2
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
CL2A (hydrazone+carbonate)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
Symmetry
Symmetric
DAR (mean)
7.6
DAR homogeneity
Heterogeneous
Plasma t½
0.7 d
Cleavage trigger
pH/acid (benzyl carbonate hydrolysis); non-enzymatic
Release control
Conditional
Hydrophilicity mask
Discrete-PEG-spacer
Conjugation site
8
Intact ADC mass (Da)
11
Formula
C50H79N9O16
Linker MW
1062.229 Da
Linker TPSA
313.81 Ų
Linker xLogP
-0.3639
ADCdb linker
LIN0ZGCUP
In-vitro stability
~50%@0.85d/human-serum (payload-release t1/2 20.3 h)
Stability note
acAb t½ ~16–23 h (mean 15.3 h Trodelvy label, 23.4 h Trop-2 mBC popPK); SN-38 free t½ 17.6–19.7 h. CL2A intentionally labile — ~50% SN-38 released in ~1 d in vitro by design (highest payload release rate of any clinically approved ADC)
05
Payload

Payload & physicochemistry

Payload profile
Payload
SN-38
Class
Topoisomerase I inhibitor
Mechanism
TopoI inhibitor
Released catabolite
SN-38 (free SN-38)
Mechanistic subtype
TopoI
Stereochem / salt
No salt/counterion specified in §11 (drug substance is the humanized IgG1κ–CL2A–SN-38 conjugate); SN-38 payload is the 20(S)/19(S)-camptothecin analog
Bystander
Partial
PAMPA rank
-
MW
392.4 Da
XLogP3
1.4
logD₇.₄
1.5
TPSA
100 Ų
pKa
8.8 pKa
Charge pH 7.4
0
H-bond donors
2
H-bond acceptors
6
IC50 (HCEC)
-
Formula
C22H20N2O5
PubChem CID
104842
ADCdb payload
PAY0ZVBAI
Plasma protein binding (%)
95 %
Hydrophobicity · logD₇.₄
hydrophilic −2+1.5+4 lipophilic
Bioactivity note
Free payload SN-38 is a potent TOP1 (DNA topoisomerase I) inhibitor. ADCdb reports SN-38 IC50 values in the picomolar-to-low-nanomolar range across cell lines (e.g., Daudi 0.13 nM, Ramos 0.4 nM, Reh 0.47 nM). For the ADC sacituzumab govitecan, ADCdb cites cell-kill IC50 of ~0.18-
06
Dosing & regimen

Dosing

RP2D dose
10 mg/kg
Schedule
D1+D8 Q3W
Route
IV
Fractionated
Yes
n at RP2D
258
Dose basis
TBW
Trial phase
Approved
Dose-OAE available
No
Tox summary basis
RP2D
07
Pharmacology

Clinical pharmacokinetics

By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews
Intact ADCTotal antibodyFree payload
Cmax
239000ng/mL
284000ng/mL
98.0ng/mL
AUC
5640000ng*h/mL
64200000ng*h/mL
3696ng*h/mL
Tmax
3.08hours
6.0hours
3.17-4.0hours
t½
23.4hours
144hours
17.6hours
CL
0.13L/h
0.0143L/h
171L/h
Vd
3.6L
1.44L
—
FDA label §12.3 Drugs@FDA reviewhover a value for dose / population / source · “+N” marks additional reported values
08
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
5 %
OAE grade 3+
0 %
OAE data status
reported
Severity (weighted)
1.5
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
-
Surface subtype
Anterior ocular-surface / lacrimal
Grading scale
Mixed
Reversibility
Reversible
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 · source-verified
Ascertainment: Symptom-driven reportingScale: MixedDenominator: RP2D⚠ Not comparable: symptom-driven ascertainment + mixed grading scale
Dose & schedule → ocular toxicity · ocular AE (any-grade) by cohort
10 mg/kg
IV Days 1 and 8 of 21-day cycle
8.82%
n=34 · SG metastatic solid tumor basket
10 mg/kg
IV Days 1 and 8 of 21-day cycle (+ magrolimab)
7.69%
n=13 · Magrolimab + SG
10 mg/kg
IV Days 1 and 8 of 21-day cycle
6.45%
n=31 · SG metastatic solid tumor basket
10 mg/kg
IV Days 1 and 8 of 21-day cycle
2.33%
n=43 · SG metastatic solid tumor basket
10 mg/kg
IV Days 1 and 8 of 21-day cycle
1.92%
n=52 · MORPHEUS-panBC SG cohort
10 mg/kg
IV Days 1 and 8 of 21-day cycle
0.37%
n=268 · TROPiCS-02
10 mg/kg
IV Days 1 and 8 of 21-day cycle
0.34%
n=296 · EVOKE-01
10 mg/kg
IV Days 1 and 8 of 21-day cycle (doses up to 10 mg/kg)
0.2%
n=495 · IMMU-132-01
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
sacituzumab-govitecan
Approval status
FDA-approved
Approval year
2020
UniProt
P09758
ADCdb ADC
DRG0EKTUN
ADCdb antibody
ANI0INHAA
ADCdb target
TAR0MIBZW
Primary source
Rugo 2022 PMC9424318 (<5% OAE)
Aliases & development codes
Trodelvy; IMMU-132
Notes
pH-dependent SN-38 lactone→carboxylate trapping reduces bystander permeability