DLYE5953A (RG-7841)

Discontinued

RG-7841; RG7841; RG 7841; DLYE-5953A; Anti-LY6E ADC

Target

Lymphocyte antigen 6E (LY6E) · LY6E

Sponsor

Genentech/Roche (with Seattle Genetics)

Indication

Refractory solid tumors (RP2D expansion: HER2-negative metastatic breast cancer, NSCLC)

Target family

GPI-anchored

RP2D dose

2.4 mg/kg

Q3W (every 3 weeks)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

3 adverse-event terms

Ocular

Any-grade

10%

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Ocular surface

Surface subtype

Corneal (off-target)

Reversibility

Unknown

Reported ocular events

Dry eye10%

Vitreous floaters1.5%

Any ocular/eye-disorder AE (grade >=3)-

G3+ 0%

Per-trial detail

Adverse events by trial

NCT02092792Phase 10.2–2.4 mg/kg (pooled) IV Q3Wn=68CTCAE v4.0PooledBto verify

Tolaney 2020 Clin Cancer Res 26(21):5588-97 Table 2 (related AE, any grade; n_events=22) PMC9899652

26 adverse-event terms · 1 system · expand a system below

Other26

Patients with ≥1 adverse event

93%

63/68

Alopecia

53%

36/68

Fatigue

46%

31/68

Nausea

38%

26/68

Peripheral neuropathy

32%

22/68

Chills

28%

19/68

Decreased appetite

28%

19/68

Peripheral sensory neuropathy

24%

16/68

Diarrhea

21%

14/68

Constipation

18%

12/68

Aspartate aminotransferase increased

16%

11/68

Back pain

15%

10/68

Alanine aminotransferase increased

13%

9/68

Mucosal inflammation

13%

9/68

Myalgia

13%

9/68

Neutropenia

13%

9/68

Pruritus

13%

9/68

Peripheral motor neuropathy

12%

8/68

Anemia

12%

8/68

Dry mouth

12%

8/68

Vomiting

12%

8/68

Arthralgia

10%

7/68

Dry eye

10%

7/68

Headache

10%

7/68

Pyrexia

10%

7/68

Parasthesia

4/68

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

MMAE

Tubulin inhibitor (microtubule polymerization 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

MLYE4489A

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

No Fc-silencing mutations reported (conventional humanized IgG1)

FcγR binding

Retained

C1q binding

Unknown

Target KD (nM)

Linker & conjugation

Linker chemistry

Linker profile

Linker

MC-vc-PAB (vedotin); Mc-Val-Cit-PABC

Class

Cleavable

Cleavage

Cleavable

Attachment

Maleimide attached to engineered cysteine

Conjugation

Site-specific cysteine

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

7.21 d

Cleavage trigger

Cathepsin B (lysosomal cysteine protease; Val-Cit dipeptide recognition)

Release control

Conditional

Hydrophilicity mask

None

Platform

THIOMAB

Conjugation site

LC-K149C

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

~100%

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor (microtubule polymerization 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 reports clinical efficacy ORR 17.76% in Phase 1 (dosing 0.20-2.40 mg/kg IV q3w; trial status terminated). No payload IC50/potency value is listed on the ADCdb ADC page or the PubChem MMAE page.

Dosing & regimen

Dosing

RP2D dose

2.4 mg/kg

Schedule

Q3W (every 3 weeks)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

ADA rate (%)

25 %

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

10 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

10 %

Blurred vision

Dominant tissue

Ocular surface

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4.0

Reversibility

Unknown

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

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

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

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

Identity & registry

Identifiers, registry & notes

ADC id

dlye5953a

Approval status

Discontinued

Approval year

UniProt

Q16553

ADCdb ADC

DRG0WOUMV

ADCdb antibody

ANI0AODFG

ADCdb target

TAR0LXDND

Primary source

Clin Cancer Res 2020;26(21):5588–5597 (PMC9899652); NCT02092792 (DLYE5953A Phase I); ADCdb DRG0WOUMV

Aliases & development codes

RG-7841; RG7841; RG 7841; DLYE-5953A; Anti-LY6E ADC

Notes

Anti-LY6E vc-MMAE ADC; Phase 1 only (terminated), no INN. Backbone clinical data from a peer-reviewed Phase I publication (Tier B); composition cross-checked against ADCdb DRG0WOUMV and ADC Review. CAVEATS: (1) DAR=4 is from ADCdb (Tier C); the publication text did not state a DAR. It is the conventional interchain-cysteine MC-vc-PAB MMAE conjugate (the preclinical mAbs 2020 paper explored THIOMAB variants, but the clinical molecule is the conventional one; DAR ~4 consistent). (2) OCULAR AMBIGUITY: the only quantified ocular PT is dry eye 10% (7/68), so oae_any_pct is set to 10 conservatively (max tabulated ocular PT). The paper states 'Thirty-seven of 68 (54%) patients developed alopecia... All but 2 patients who experienced alopecia concurrently experienced ocular AEs,' which could be read to imply a large fraction had concurrent (mostly untabulated, low-grade) ocular AEs — but NO aggregate any-grade ocular percentage is stated anywhere, and both the primary abstract and the Oncologist 2024 ADC-ocular review characterize ocular AEs as 'not prominent... all grades 1-2.' All ocular AEs grade 1-2 → oae_g3plus_pct=0 (documented). (3) N: publication safety population N=68; RP2D (2.4 mg/kg Q3W) expansion cohort n=55 (29 metastatic breast cancer, 25 NSCLC, 1 ovarian). ClinicalTrials.gov NCT02092792 shows hasResults=false and an outdated registry enrollment of 42 — no AE data posted there. (4) Linker physchem and MMAE payload values are taken from the identical shared linker LIN0SQEDQ and the standard MMAE warhead used by the DB's polatuzumab vedotin / enfortumab vedotin rows (same MC-vc-PAB vedotin chemistry). Identifiers: ADC=DLYE5953A/RG-7841; antibody=MLYE4489A.