Sacituzumab govitecan

FDA-approved

Trodelvy; IMMU-132

Target

TROP-2 · TACSTD2

Sponsor

Immunomedics/Gilead

Indication

TACSTD2+ TNBC / urothelial

Target family

TACSTD / EpCAM-TROP

RP2D dose

10 mg/kg

D1+D8 Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

29 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

65.43%

Limbus

Express.

73.31%

Conjunctiva

Express.

86.39%

Lens

Express.

Retina / RPE

Express.

0 nTPM

Dominant tissue

Surface subtype

Anterior ocular-surface / lacrimal

Reversibility

Reversible

Reported ocular events

Eye infection16.67%

non-seriousn=6

Vitreous floaters4%

non-seriousn=25

Visual impairment4%

non-seriousn=25

Blepharospasm4%

non-seriousn=25

Erythema of eyelid4%

non-seriousn=25

Eye disorders - Other, specify3.23%

non-seriousn=31

Lacrimation increased2.26%

poolednon-seriousn=354

Dry eye2.26%

poolednon-seriousn=354

Vision blurred1.41%

poolednon-seriousn=354

Cataract1.13%

poolednon-seriousn=354

Conjunctivitis0.85%

poolednon-seriousn=354

Visual acuity reduced0.85%

poolednon-seriousn=354

Eyelid oedema0.85%

poolednon-seriousn=354

Blepharitis0.56%

poolednon-seriousn=354

Diplopia0.28%

poolednon-seriousn=354

Intraocular pressure increased0.28%

poolednon-seriousn=354

Retinal vein occlusion0.28%

pooledseriousn=354

Serous retinal detachment0.28%

pooledseriousn=354

Central serous chorioretinopathy0.28%

poolednon-seriousn=354

Macular thickening0.28%

poolednon-seriousn=354

Ocular hyperaemia0.28%

poolednon-seriousn=354

Photopsia0.28%

poolednon-seriousn=354

Xerophthalmia0%

non-seriousn=30

Ocular discomfort0%

non-seriousn=30

Episcleritis0%

non-seriousn=30

Eye pruritus0%

non-seriousn=30

Eyelid ptosis0%

non-seriousn=30

Conjunctivitis viral0%

non-seriousn=30

Eye pain0%

non-seriousn=55

Per-trial detail

Adverse events by trial

Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based TreatmePHASE1|PHASE2real-worldn=30CTCAE NR (ClinicalTrials.govPooledC

ClinicalTrials.gov NCT03869190 posted results, adverse events module (serious; 1/297 pooled across arms)

479 adverse-event terms · 22 systems · expand a system below

Infections60

Sepsis

16.67%serious

5/30

Urinary tract infection

16.67%non-serious

5/30

Bacillus Calmette-Guerin infection

3.33%serious

1/30

Septic shock

3.33%serious

1/30

COVID-19

3.33%non-serious

1/30

Nasopharyngitis

3.33%non-serious

1/30

Oral candidiasis

3.33%non-serious

1/30

Oral herpes

3.33%non-serious

1/30

Perineal abscess

3.33%non-serious

1/30

Peritonitis bacterial

3.33%non-serious

1/30

Pharyngitis

3.33%non-serious

1/30

Pharyngotonsillitis

3.33%non-serious

1/30

Respiratory tract infection

3.33%non-serious

1/30

Upper respiratory tract infection

3.33%non-serious

1/30

Abdominal abscess

0%serious

0/30

Abdominal infection

0%serious

0/30

Abscess limb

0%serious

0/30

Bacteraemia

0%non-serious

0/30

Bacterial infection

0%non-serious

0/30

Escherichia urinary tract infection

0%serious

0/30

Gallbladder abscess

0%serious

0/30

Gastroenteritis

0%serious

0/30

Infected fistula

0%serious

0/30

Kidney infection

0%non-serious

0/30

Metapneumovirus infection

0%serious

0/30

Pneumonia

0%non-serious

0/30

Pyelonephritis

0%non-serious

0/30

Soft tissue infection

0%serious

0/30

Ureteritis

0%serious

0/30

Urinary tract infection enterococcal

0%serious

0/30

Urosepsis

0%non-serious

0/30

Wound sepsis

0%serious

0/30

Abdominal wall abscess

0%non-serious

0/30

Abscess jaw

0%non-serious

0/30

Bacterial disease carrier

0%non-serious

0/30

Cellulitis

0%non-serious

0/30

Clostridium difficile infection

0%non-serious

0/30

Coronavirus infection

0%non-serious

0/30

Cystitis

0%non-serious

0/30

Device related infection

0%non-serious

0/30

Diarrhoea infectious

0%non-serious

0/30

Folliculitis

0%non-serious

0/30

Fungal skin infection

0%non-serious

0/30

Gastrointestinal infection

0%non-serious

0/30

Groin infection

0%non-serious

0/30

Herpes zoster

0%non-serious

0/30

Influenza

0%non-serious

0/30

Klebsiella urinary tract infection

0%non-serious

0/30

Lower respiratory tract infection

0%non-serious

0/30

Oropharyngeal candidiasis

0%non-serious

0/30

Otitis media

0%non-serious

0/30

Post procedural infection

0%non-serious

0/30

Respiratory syncytial virus infection

0%non-serious

0/30

Respiratory tract infection viral

0%non-serious

0/30

Scabies

0%non-serious

0/30

Skin infection

0%non-serious

0/30

Tooth infection

0%non-serious

0/30

Vaginal infection

0%non-serious

0/30

Vascular device infection

0%non-serious

0/30

Vulvovaginal mycotic infection

0%non-serious

0/30

GI44

Neurologic (other)39

Dermatologic33

Investigations30

Injury29

General27

Pulmonary27

Musculoskeletal26

Renal25

Metabolic23

Vascular18

Ocular17

Lacrimation increased

0%non-serious

0/30

Vitreous floaters

0%non-serious

0/30

Xerophthalmia

0%non-serious

0/30

Ocular discomfort

0%non-serious

0/30

Vision blurred

0%non-serious

0/30

Visual impairment

0%non-serious

0/30

Visual acuity reduced

0%serious

0/30

Blepharitis

0%non-serious

0/30

Cataract

0%non-serious

0/30

Diplopia

0%non-serious

0/30

Dry eye

0%non-serious

0/30

Episcleritis

0%non-serious

0/30

Eye pruritus

0%non-serious

0/30

Eyelid ptosis

0%non-serious

0/30

Conjunctivitis

0%non-serious

0/30

Conjunctivitis viral

0%non-serious

0/30

Intraocular pressure increased

0%non-serious

0/30

Hematologic16

Other14

Cardiac13

Psychiatric12

Neoplasms7

Ear6

Hepatic6

Endocrine5

Immune2

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

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

Antibody

Antibody & Fc engineering

Antibody

hRS7 (sacituzumab)

Isotype

IgG1

Origin

Humanized

Fc modifications

None^inferred

Glycoengineering

Standard^inferred

Effector silencing

None^inferred

FcγR binding

Retained

C1q binding

Retained^inferred

Target KD (nM)

1.2

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^locator?

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^unver.

Formula

C50H79N9O16

Linker MW

1062.229 Da

Linker TPSA

313.81 Å²

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)

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

392.4 Da

XLogP3

1.4

logD₇.₄

1.5

TPSA

100 Å²

pKa

8.8 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

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-

Dosing & regimen

Dosing

RP2D dose

10 mg/kg

Schedule

D1+D8 Q3W

Route

Fractionated

Yes

n at RP2D

258

Dose basis

TBW

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Pharmacology

Clinical pharmacokinetics

By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews

	Intact ADC	Total antibody	Free 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

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

5 %

OAE grade 3+

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^locator?

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

—

16.67%

n=6 · A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Par

—

7.27%

n=55 · ELEVATE TNBC

—

n=25 · Rollover Study in Participants With Metastatic Solid Tumors Benefiting From Ther

—

3.23%

n=31 · Sacituzumab Govitecan in Patients With Metastatic Castration-Resistant Prostate

—

2.26%

n=354 · Morpheus Lung

—

2.24%

n=223 · TROPiCS-03

—

n=30 · Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatme

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

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