Serclutamab talirine (ABBV-321, EGFR, PBD/SGD-1882)

Discontinued

ABBV-321; ABBV321; Ser-T

Target

Epidermal growth factor receptor (EGFR) · EGFR

Sponsor

AbbVie

Indication

Advanced EGFR-overexpressing solid tumors (incl. glioblastoma)

Target family

Receptor tyrosine kinase

RP2D dose

0.025 mg/kg Q4W (50 ug/kg loading dose cycle 1, then 25 ug/kg; i.e. 0.05 -> 0.025 mg/kg)

Once every 4 weeks (Q4W)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

6 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

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

Conjunctiva

Surface subtype

Mixed

Reversibility

Reversible

Reported ocular events

Conjunctivitis7%

G3+ 0%

Eye pruritus3%

Keratitis2%

Corneal erosion2%

Dry eye2%

Blurred vision2%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Peptide

Cleavable

DAR

Payload

SGD-1882 (PBD dimer)

DNA minor-groove interstrand crosslinker (alkylation) -> DNA damage, cell-cycle arrest, apoptosis

Linker structureC18H27N3O6

[H]OC(=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])N1C(=O)C([H])=C([H])C1=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H]

Payload structureC42H39N5O7

COC1=CC=C(C=C1)C2=CN3[C@@H](C2)C=NC4=CC(=C(C=C4C3=O)OC)OCCCOC5=C(C=C6C(=C5)N=C[C@@H]7CC(=CN7C6=O)C8=CC=C(C=C8)N)OC

Antibody

Antibody & Fc engineering

Antibody

Serclutamab (AM-1-ABT-806; affinity-matured ABT-806, binds a cryptic/conformational EGFR epitope)

Isotype

IgG1

Origin

Humanized

Fc modifications

S239C

Glycoengineering

Effector silencing

None reported (intact humanized IgG1 Fc; S239C engineered cysteine is a conjugation handle, not an Fc-silencing mutation)

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

Maleimidocaproyl-L-valine-L-alanine (Mc-Val-Ala)

Class

Peptide

Cleavage

Cleavable

Attachment

Site-specific (engineered Cys)

Conjugation

Site-specific via engineered cysteine (S239C); EC-mAb/talirine platform; DAR 2

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

Cleavage trigger

Cathepsin B (lysosomal protease; Val-Ala dipeptide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C18H27N3O6

Linker MW

381.429 Da

Linker TPSA

132.88 Å²

Linker xLogP

0.2019

ADCdb linker

LIN0ENDIF

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

SGD-1882 (PBD dimer)

Class

PBD dimer

Mechanism

DNA minor-groove interstrand crosslinker (alkylation) -> DNA damage, cell-cycle arrest, apoptosis

Released catabolite

PBD dimer SGD-1882 (released after cathepsin-B cleavage of Val-Ala)

Mechanistic subtype

DNA-crosslinker-PBD

Stereochem / salt

L-Val-L-Ala (2S,2S) dipeptide linker; PBD dimer free base (no salt)

Bystander

Yes

PAMPA rank

725.8 Da

XLogP3

3.9

logD₇.₄

TPSA

138 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C42H39N5O7

PubChem CID

45257190

ADCdb payload

PAY0AKDAM

Bioactivity note

ADCdb reports ADC potency (IC50) ranging from ~15 pM (SW48 colon cells) to ~28.4 nM (HCT-15 colon cells) across 38 cell-line experiments; clinical NCT03234712 reported 1 partial response of 24 patients. SGD-1882 PBD-dimer warhead acts by DNA minor-groove interstrand cross-linking

Dosing & regimen

Dosing

RP2D dose

0.025 mg/kg Q4W (50 ug/kg loading dose cycle 1, then 25 ug/kg; i.e. 0.05 -> 0.025 mg/kg)

Schedule

Once every 4 weeks (Q4W)

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

7 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

2.1

Keratopathy

2 %

Conjunctival

7 %

Dry eye

2 %

Blurred vision

2 %

Dominant tissue

Conjunctiva

Surface subtype

Mixed

Grading scale

CTCAE v4

Reversibility

Reversible

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

serclutamab-talirine

Approval status

Discontinued

Approval year

UniProt

P00533

ADCdb ADC

DRG0CXFTH

ADCdb antibody

ANI0QFTKC

ADCdb target

TAR0UYFIF

Primary source

Phase 1 FIH, Neuro-Oncol Adv 2022;5(1):vdac183 (PMC9940695 / PMID 36814898); NCT03234712

Aliases & development codes

ABBV-321; ABBV321; Ser-T

Notes

Serclutamab talirine (ABBV-321 / Ser-T) = humanized affinity-matured anti-EGFR IgG1 antibody (Serclutamab = AM-1-ABT-806, an affinity-matured ABT-806 that binds a cryptic/conformational EGFR epitope) conjugated site-specifically via an engineered S239C cysteine and a maleimidocaproyl-Val-Ala cathepsin-B-cleavable linker (Mc-Val-Ala) to the PBD dimer SGD-1882, DAR 2. Same payload + linker (talirine/EC-mAb platform) as vadastuximab talirine. Source 1 (ADCdb DRG0CXFTH + linker LIN0ENDIF) supplied composition + linker physchem (C18H27N3O6, MW 381.429, TPSA 132.88, xLogP 0.2019). Source 2 (Phase 1 FIH NCT03234712; Neuro-Oncol Adv 2022;5(1):vdac183, PMC9940695): n=62 (43 dose-escalation + 19 expansion; glioblastoma n=24 plus CRC/NSCLC/HNSCC/other EGFR-overexpressing solid tumors), IV Q4W, doses 5-50 ug/kg; RP2D = 50 ug/kg loading dose x1 then 25 ug/kg Q4W (expansion n=19); single DLT = Gr3 AST/ALT at 20 ug/kg; CTCAE v4.03. Safety hepatic-dominant (GGT 21%, ALT 18%, AST 16% TRAE; Gr3+ AST 10%/GGT 11%/ALT 8%) plus thrombocytopenia (18% TRAE, Gr3+ 7%); pneumonitis (PBD/ILD-class) seen. Peripheral neuropathy and infusion reactions NOT reported; neutropenia not among common AEs. OCULAR: assessed and PRESENT but mild and all Gr1-2 - conjunctivitis 7% (4/62; 3 Gr1 + 1 Gr2 lasting 117d, ongoing at study end), eye pruritus 3% (2/62), and ONE patient (2%) with a corneal/visual cluster (keratitis + corneal erosion + corneal toxicity + dry eye + blurred vision). No Gr3+ ocular events. oae_any_pct=7 is the max single ocular PT (conjunctivitis); union across distinct ocular PTs is ~11% (~7 distinct patients), consistent with the 7-11% hint. Subtype coded Mixed (conjunctival dominant + a corneal + visual cluster). Ocular AEs were reported pooled across all dose levels, not dose-stratified. Authors explicitly note the PBD payload is NOT associated with the corneal epitheliopathy caused by the mafodotin (MMAF) payload of earlier-generation EGFR ADCs. Source 3 (PubChem CID 45257190, SGD-1882, C42H39N5O7): MW 725.8, XLogP3 3.9, TPSA 138, charge 0 (neutral); bystander activity assigned Yes as a PBD-dimer class property (tier C, not directly measured in these sources). logD7.4 and pKa not available in public sources (left blank). Program later terminated (ADCdb status: Phase 1, Terminated).