Aprutumab ixadotin

Discontinued

BAY 1187982

Target

FGFR2 · FGFR2

Sponsor

Bayer

Indication

FGFR2+ solid tumors

Target family

Receptor tyrosine kinase

RP2D dose

0.2 mg/kg (Q3W MTD; trial terminated, no formal RP2D)

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

5 adverse-event terms

Ocular

Any-grade

40%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

20%

Express.

58.38%

Limbus

Express.

77.56%

Conjunctiva

Express.

74.29%

Lens

Express.

Retina / RPE

Express.

0.7 nTPM

Off-target signature

20% corneal toxicity, yet the FGFR2 target is detected in only 58.38% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Corneal deposits20%

G3+ 0%n=20

Corneal epithelial microcysts15%

G3+ 5%n=20

Vision blurred5%

n=20

Retinal haemorrhage-

Ocular discomfort-

Per-trial detail

Adverse events by trial

NCT02368951Phase 10.1-1.3 mg/kg (pooled across 5 escalation cohorts) IV day 1 of every 21-day cycle (Q3W)n=20CTCAE 4.03PooledBto verify

Kim 2019 Target Oncol PMID:31502117

36 adverse-event terms · 3 systems · expand a system below

Other31

Aspartate aminotransferase increased

60%G3+ 15%

12/20

Thrombocytopenia

50%G3+ 25%

10/20

Anaemia

30%G3+ 10%

6/20

Fatigue

30%G3+ 0%

6/20

Nausea

25%G3+ 0%

5/20

Pyrexia

25%G3+ 0%

5/20

Alanine aminotransferase increased

25%G3+ 5%

5/20

Blood alkaline phosphatase increased

25%G3+ 15%

5/20

Decreased appetite

25%G3+ 5%

5/20

Abdominal pain

20%G3+ 0%

4/20

Corneal deposits

20%G3+ 0%

4/20

Corneal epithelial microcysts

15%G3+ 5%

3/20

Dyspepsia

15%G3+ 0%

3/20

Vomiting

15%G3+ 5%

3/20

Urinary tract infection

15%G3+ 5%

3/20

Hypoalbuminaemia

15%G3+ 0%

3/20

Cough

15%G3+ 0%

3/20

Abdominal distension

10%G3+ 0%

2/20

Ascites

10%G3+ 5%

2/20

Blood cholesterol increased

10%G3+ 0%

2/20

Blood creatinine increased

10%G3+ 0%

2/20

Blood fibrinogen increased

10%G3+ 0%

2/20

Brain natriuretic peptide increased

10%G3+ 0%

2/20

Fibrin D-dimer increased

10%G3+ 0%

2/20

Lipase increased

10%G3+ 0%

2/20

White blood cell count decreased

10%G3+ 0%

2/20

Dehydration

10%G3+ 5%

2/20

Hypercalcaemia

10%G3+ 0%

2/20

Proteinuria

10%G3+ 10%

2/20

Epistaxis

10%G3+ 0%

2/20

Productive cough

10%G3+ 0%

2/20

Overall/Summary4

Ocular1

Any ocular event

40%

8/20

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Non-cleavable

4.1

DAR

Payload

Auristatin W

Tubulin inhibitor

Linker structureC6H12O2

CCCCCC(=O)O

Payload structureC45H73N7O8

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N4CCCCO4)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

anti-FGFR2 (aprutumab)

Isotype

IgG1

Origin

Human

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Dev code

BAY 1179470

Epitope / domain

N-terminal extracellular epitope of FGFR2

Linker & conjugation

Linker chemistry

Linker profile

Linker

Lys non-cleavable (auristatin W)

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Lysine

Conjugation

Conventional Lys (non-cleavable)

Symmetry

Asymmetric

DAR (mean)

4.1

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

Cell line

CHO

Formula

C6H12O2

Linker MW

116.16 Da

Linker TPSA

37.3 Å²

Linker xLogP

1.6513

ADCdb linker

LIN0IUSXC

In-vitro stability

Stability note

Lys-NHS non-cleavable to auristatin W; Phase 1 terminated at MTD 0.2 mg/kg below therapeutic threshold (Kim Target Oncol 2019 N=20); Sommer MCT 2016 reports off-target toxicity from circulating linker-payload metabolite in cyno but no clinical t½ in d in either source

Payload

Payload & physicochemistry

Payload profile

Payload

Auristatin W

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

BAY 1159184 (auristatin W-derived toxophore metabolite)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

PAMPA rank

746 Da

XLogP3

2.6

logD₇.₄

1.5

TPSA

158 Å²

pKa

3.5 pKa

Charge pH 7.4

Zwitterion

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C45H73N7O8

PubChem CID

86678408

ADCdb payload

PAY0PBONE

Hydrophobicity · logD₇.₄

hydrophilic −2+1.5+4 lipophilic

Bioactivity note

Auristatin W is a microtubule-inhibiting auristatin (dolastatin-10 analog); ADCdb lists payload mechanism as 'Microtubule (MT)' disruption. No discrete payload IC50 reported on ADCdb/PubChem. Clinically (first-in-human phase I, PMID 31502117) the ADC was terminated for poor toler

Dosing & regimen

Dosing

RP2D dose

0.2 mg/kg (Q3W MTD; trial terminated, no formal RP2D)

Schedule

Q3W

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

40 %

OAE grade 3+

5 %

OAE data status

reported

Severity (weighted)

15.5

Keratopathy

20 %

Conjunctival

Dry eye

Blurred vision

5 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4.03

Reversibility

Reversible

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

Cornea (central)

58.38 %

Cornea (limbal)

77.56 %

Conjunctiva

74.29 %

RPE

Retina (HPA)

0.7 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort

0.1-1.3 mg/kg (pooled across 5 escalation cohorts)

IV day 1 of every 21-day cycle (Q3W)

40%

n=20 · NCT02368951

0.1-1.3 mg/kg (pooled; events only at 0.8 and 1.3 mg/kg)

IV Q3W (day 1 of 21-day cycle)

20%

n=20 · BAY 1187982 FIH

0.1-1.3 mg/kg (pooled across 5 escalation cohorts)

IV day 1 of every 21-day cycle (Q3W)

n=20 · NCT02368951

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

aprutumab-ixadotin

Approval status

Discontinued

Approval year

UniProt

P21802

ADCdb ADC

DRG0JJEUT

ADCdb antibody

ANI0KNFWI

ADCdb target

TAR0OXEAL

Primary source

Kim Target Oncol 2019

Aliases & development codes

BAY 1187982

Notes

Trial terminated early due to off-target coagulation toxicity. V3.1: RP2D corrected 0.7→0.2 mg/kg Q3W per Kim Target Oncol 2019 (0.7 not among tested cohorts 0.1/0.2/0.4/0.8/1.3). Corneal events: 15% microcysts + 20% deposits (distinct events).