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

0 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Unknown

↳

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

Unknown

Reversibility

Unknown

Reported ocular events

No granular adverse-event rows recorded for this system.

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

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

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

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

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

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

Unknown

Grading scale

Mixed

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 · source-verified

Ascertainment: Systematic eye examsScale: MixedDenominator: RP2D⚠ OAE rate not directly comparable across trials

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