Samrotamab vedotin (ABBV-085)

Discontinued

ABBV-085; ABBV 085; ABBV085; PR-1498487-MMAE

Target

LRRC15 (leucine-rich repeat-containing protein 15) · LRRC15

Sponsor

AbbVie

Indication

Sarcoma (osteosarcoma, UPS) and advanced solid tumors

Target family

Other

RP2D dose

3.6 mg/kg

Q2W (every 14 days)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

1 adverse-event term

Ocular

Any-grade

24.4%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Surface subtype

Visual

Reversibility

Reversible

Reported ocular events

Vision blurred24.4%

G3+ 0%n=78

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

MMAE

Tubulin inhibitor

Linker structureC28H40N6O7

[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H])c([H])c1[H]

Payload structureC39H67N5O7

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

Samrotamab

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

MC-vc-PAB (vedotin)

Class

Cleavable

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE (free / unconjugated monomethyl auristatin E)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

ADCdb ADC page reports no payload IC50. ADC-level activity noted: clinical ORR ranged ~2.1%-20% depending on tumor type/dose; preclinical tumor growth inhibition (TGI) 27.9%-100% in PDX models. Target therapeutic class listed as Microtubule (MT) (consistent with MMAE tubulin inhi

Dosing & regimen

Dosing

RP2D dose

3.6 mg/kg

Schedule

Q2W (every 14 days)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

24.4 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

7.32

Keratopathy

Conjunctival

Dry eye

Blurred vision

24.4 %

Dominant tissue

Surface subtype

Visual

Grading scale

CTCAE (unversioned)

Reversibility

Reversible

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE (unversioned)Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

samrotamab-vedotin

Approval status

Discontinued

Approval year

UniProt

Q8TF66

ADCdb ADC

DRG0OPFVY

ADCdb antibody

ANI0VVOSK

ADCdb target

TAR0QEXPC

Primary source

First-in-Human Phase I ABBV-085, Clin Cancer Res 2021;27(13):3556-66 (PMID 33820780; DOI 10.1158/1078-0432.CCR-20-4513); NCT02565758

Aliases & development codes

ABBV-085; ABBV 085; ABBV085; PR-1498487-MMAE

Notes

Anti-LRRC15 (stromal/CAF antigen) humanized IgG1-kappa MMAE ADC, cysteine-conjugated DAR 2, MC-vc-PAB (vedotin) linker (LIN0SQEDQ, identical to brentuximab/enfortumab vedotin in our DB). AbbVie; development discontinued (ADCdb: Phase 1 terminated). FIH Phase 1 NCT02565758 (Clin Cancer Res 2021;27:3556-66, PMID 33820780): 85 enrolled; 0.3-6.0 mg/kg Q2W IV; RP2D 3.6 mg/kg (n=45). Reported AE percentages are based on the N=78 monotherapy safety population (pooled across doses), which is the only grade-resolved tabulation publicly available; n_rp2d set to 78 to match that denominator (3.6 mg/kg cohort itself = 45). PRIORITY OCULAR SIGNAL: blurred vision 19/78 (24.4%), all grade 1/2, reversible on discontinuation, 0% G3+; classified ocular_surface_subtype = Visual because only the blurred-vision symptom is itemized (no corneal/conjunctival slit-lamp findings or dry-eye/keratopathy PTs were reported). The paper's narrative loosely states overall ocular toxicity ~25-30%, but 24.4% is the exact figure. Other firm data: peripheral neuropathy 24/78 (31%, dose-related, 1 G3+ at 3.6 mg/kg); anaemia G3+ 14.1% (11/78, most common G3+); overall G3+ TEAE 56/78 (71.8%); fatigue 48.7% (constitutional, no organ-enum match so not added as a toxicity row). DATA GAPS (behind AACR/ASCO paywall, left blank per convention, not zero): exact %s for nausea and decreased appetite (named as most-common TRAEs but unquantified), neutropenia, thrombocytopenia, any-grade anaemia, hepatic AST/ALT, pulmonary/ILD, and infusion reactions. CTCAE version not stated in retrieved sources. Payload physchem = standard MMAE values; linker physchem confirmed from ADCdb LIN0SQEDQ.