Cetuximab saratolacan

Approved (ex-US)

Akalux; RM-1929; ASP-1929

Target

EGFR · EGFR

Sponsor

Rakuten Medical/Aspyrian

Indication

EGFR+ HNSCC (photoimmunotherapy)

Target family

Receptor tyrosine kinase

RP2D dose

640 mg/m²

Single dose + 690 nm laser; repeat Q4WRP2D

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.

89.35%

Limbus

Express.

97.58%

Conjunctiva

Express.

93.02%

Lens

Express.

Retina / RPE

Express.

83.36%

9.4 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

No granular adverse-event rows recorded for this system.

Construct

Molecular anatomy

Antibody

IgG1

Chimeric

Linker

Non-cleavable

Cleavable

DAR

Payload

IRDye700DX

Photochemical (690 nm NIR ROS)

Linker structureC14H22N2O7

[H]OC([H])([H])C([H])([H])C([H])([H])OC(=O)N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(=O)ON1C(=O)C([H])([H])C([H])([H])C1=O

Payload structureC74H96N12Na4O27S6Si3

C[Si](C)(CCC[N+](CCCS(=O)(=O)[O-])(CCCS(=O)(=O)[O-])CCCS(=O)(=O)[O-])O[Si]1(N2C3=C4C=CC=CC4=C2N=C5C6=C(C=CC=C6OCCCOC(=O)NCCCCCC(=O)ON7C(=O)CCC7=O)C(=N5)N=C8N1C(=NC9=NC(=N3)C1=CC=CC=C19)C1=CC=CC=C18)O[Si](C)(C)CCC[N+](CCCS(=O)(=O)[O-])(CCCS(=O)(=O)[O-])CCCS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+]

Antibody

Antibody & Fc engineering

Antibody

cetuximab

Isotype

IgG1

Origin

Chimeric

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

NHS ester to Lys (IR700)

Class

Non-cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (NHS)

Symmetry

N/A

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Photoactivated (non-cleavable)

Release control

N/A

Hydrophilicity mask

Sulfonate

Formula

C14H22N2O7

Linker MW

330.337 Da

Linker TPSA

122.24 Å²

Linker xLogP

0.2626

ADCdb linker

LIN0KIZQG

In-vitro stability

Stability note

Photoimmunotherapy mechanism — IR700 photosensitizer is inert without 690 nm illumination; eye is never illuminated; no warhead release in plasma; t½ axis is not toxicity-relevant for this drug

Payload

Payload & physicochemistry

Payload profile

Payload

IRDye700DX

Class

Photosensitizer

Mechanism

Photochemical (690 nm NIR ROS)

Released catabolite

None - photoactivated mechanism; no circulating cytotoxic catabolite is released. IRDye700DX (sarotalocan) is a photosensitizer that is pharmacologically inert without 690 nm NIR light and is bound to cetuximab via a non-cleavable conjugate; cytotoxicity arises only from in-situ photochemistry at the illuminated tumour, not from a diffusible small-molecule payload.

Mechanistic subtype

Other

Stereochem / salt

Tetrasodium salt (Na+ counter-ions on the sulfonate groups of the sarotalocan/IRDye700DX silicon-phthalocyanine dye); silicon centre octahedrally coordinated, OC-6-13 isomer; achiral dye with no defined R/S stereocentres

Bystander

PAMPA rank

1954.2 Da

XLogP3

logD₇.₄

-5

TPSA

606 Å²

pKa

Charge pH 7.4

-4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C74H96N12Na4O27S6Si3

PubChem CID

102004325

ADCdb payload

PAY0EJBOG

Hydrophobicity · logD₇.₄

hydrophilic −2-5+4 lipophilic

Bioactivity note

ADCdb payload page (PAY0EJBOG) reports no direct free-payload IC50; it cites EC50 values for an unrelated EGFR-PIT conjugate (ARB102-IR700), not cetuximab-saratolacan: LoVo 0.12 ug/mL, SW480 49.00 ng/mL, SNU-C1 74.00 ng/mL, AsPC-1 86.00 ng/mL. Mechanism: IRDye700DX is a silicon-p

Dosing & regimen

Dosing

RP2D dose

640 mg/m²

Schedule

Single dose + 690 nm laser; repeat Q4W

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0 %

OAE grade 3+

0 %

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

None

Grading scale

CTCAE v4

Reversibility

Unknown

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

Cornea (central)

89.35 %

Cornea (limbal)

97.58 %

Conjunctiva

93.02 %

RPE

83.36 %

Retina (HPA)

9.4 nTPM

Cross-trial comparability

Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

cetuximab-saratolacan

Approval status

Approved (ex-US)

Approval year

2020

UniProt

P00533

ADCdb ADC

DRG0DXROV

ADCdb antibody

ANI0GYJQM

ADCdb target

TAR0UYFIF

Primary source

Cognetti Head Neck 2021 (PMID 34626024); Tahara Int J Clin Oncol 2021

Aliases & development codes

Akalux; RM-1929; ASP-1929

Notes

Mechanistic outlier: IR700 inert without 690 nm NIR illumination; eye never illuminated. V3.1: n=30 (Cognetti Phase 2a at 640 mg/m²). DAR 3.0 not verifiable from sources — flagged for v3.2.