Iladatuzumab vedotin

Investigational

DCDS0780A; anti-CD79B-MMAE THIOMAB

Target

CD79B · CD79B

Sponsor

Genentech/Roche

Indication

CD79B+ NHL

Target family

Immunoglobulin superfamily

RP2D dose

4.8 mg/kg

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

47%

G3+

RP2D

sagittal schematic · Mixed

↳

Tissues shaded by reported adverse-event rate.

Cornea

28%

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

0 nTPM

Off-target signature

28% corneal toxicity, yet the CD79B target is detected in only 0% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Ocular surface

Surface subtype

Corneal (off-target)

Reversibility

Mixed

Reported ocular events

Ocular toxicity (any related ocular event; AESI composite)47%

n=60

Vision blurred35%

n=60

Corneal deposits28%

n=60

Keratitis10%

n=60

Ocular toxicity (related ocular event; AESI composite)-

G3+ 8%n=60

Per-trial detail

Adverse events by trial

NCT02453087 (DCDS0780A Ph Ia/Ib FIH)Phase 10.3-4.8 mg/kg (RP2D 4.8 mg/kg) Q3W IVn=60CTCAE v4.0RP2DB

Herrera Clin Cancer Res 2022;28:1294-1301 (PMID 34980599)

17 adverse-event terms · 8 systems · expand a system below

Ocular5

Ocular toxicity (any related ocular event; AESI composite)

47%

28/60

Vision blurred

35%

21/60

Corneal deposits

28%

17/60

Keratitis

10%

6/60

Ocular toxicity (related ocular event; AESI composite)

—G3+ 8%

Hematologic3

GI2

Metabolic2

Neurologic-PN2

General1

Hepatic1

Pulmonary1

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

anti-CD79B (iladatuzumab)

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

0.3

Dev code

MCDS0593A

Epitope / domain

CD79B N-terminal extracellular Ig-like domain

Linker & conjugation

Linker chemistry

Linker profile

Linker

THIOMAB MC-vc-PAB

Class

Cleavable

Cleavage

Cleavable

Attachment

Site-specific (engineered Cys)

Conjugation

THIOMAB

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

7.0 d

Cleavage trigger

Cathepsin B (Val-Cit)

Release control

Conditional

Hydrophilicity mask

None

Platform

THIOMAB

Conjugation site

HC-A114C

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Stability note

Inherited from THIOMAB MC-vc-PAB class — site-specific engineered Cys gives ADC t½ ~2–3× longer than conventional vedotin at stable sites (Shen Nat Biotechnol 2012; Strop Chem Biol 2013). Herrera CCR 2022 Ph1 N=60 reports linear PK ≥1.2 mg/kg with similar CL for acMMAE and total antibody but does not give numeric t½ in d in the open-access full text

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE

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

MMAE free-payload cytotoxicity IC50 (ADCdb PAY0FSXOW): 0.25 nM in Granta-519 (mantle cell lymphoma) and SU-DHL-4 (DLBCL); 0.54 nM in BJAB (Burkitt); 0.13±0.02 nM in MDA-MB-231 and 0.66±0.06 nM in MDA-MB-468 (breast adenocarcinoma). Payload primary target = microtubules (tubulin p

Dosing & regimen

Dosing

RP2D dose

4.8 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

ADA rate (%)

2 %

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

47 %

OAE grade 3+

8 %

OAE data status

reported

Severity (weighted)

19.7

Keratopathy

28 %

Conjunctival

Dry eye

Blurred vision

35 %

Dominant tissue

Ocular surface

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4.0

Reversibility

Mixed

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

Cornea (central)

0 %

Cornea (limbal)

0 %

Conjunctiva

0 %

RPE

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ Not comparable: symptom-driven ascertainment

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

0.3-4.8 mg/kg +/- rituximab

IV Q3W

47%

n=60 · DCDS0780A ph1a/1b

0.3-4.8 mg/kg (RP2D 4.8 mg/kg)

Q3W IV

28%

n=60 · NCT02453087 (DCDS0780A Ph Ia/Ib FIH)

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

iladatuzumab-vedotin

Approval status

Investigational

Approval year

UniProt

P40259

ADCdb ADC

DRG0AZRNL

ADCdb antibody

ANI0MRCNB

ADCdb target

TAR0KZVDX

Trial (NCT)

NCT02453087

Primary source

Herrera CCR 2022 PMID 34980599

Aliases & development codes

DCDS0780A; anti-CD79B-MMAE THIOMAB

Notes

Same target+payload as polatuzumab vedotin (5% OAE) but 38pp higher OAE → conjugation format effect. V3.1: RP2D corrected 2.4→4.8 mg/kg; OAE any 43→47; G3+ 8.0 (was blank); blurred vision 35%; corneal deposits 28%. THIOMAB position V205C NOT stated in Herrera 2022 — corrected to 'position not disclosed'.