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Zilovertamab vedotin

Investigational
MK-2140; anti-ROR1-MMAE
Sponsor
VelosBio/Merck
Indication
ROR1+ NHL
Target family
Receptor tyrosine kinase
RP2D dose
2.5 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
1 adverse-event term

Ocular

Any-grade
0%
G3+
0%
RP2D
sagittal schematic · Unknown
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
1.09%
Limbus
AE
-
Express.
3.42%
Conjunctiva
AE
-
Express.
4.09%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
Dominant tissue
-
Surface subtype
None
Reversibility
Unknown
Reported ocular events
Ocular toxicity (any; keratopathy/dry eye/blurred vision)0%
n=32
Per-trial detail

Adverse events by trial

MK-2140-002 / VLS-101 (NCT04504916)Phase 21.75 mg/kg Days 1 and 8 of each 21-day cycle (Q2/3W)n=32CTCAE 5.0PooledB
CT.gov NCT04504916 posted results, adverse events module (other/non-serious AE; MedDRA 23.1) NCT04504916
21 adverse-event terms · 13 systems · expand a system below
Investigations4
Alanine aminotransferase increased
6.25%
2/32
Blood phosphorus increased
6.25%
2/32
Blood sodium decreased
6.25%
2/32
White blood cell count decreased
6.25%
2/32
Musculoskeletal4
Neurologic (other)3
Hematologic1
Cardiac1
GI1
General1
Infections1
Injury1
Metabolic1
Pulmonary1
Dermatologic1
Vascular1
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
Cleavable
4
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
03
Antibody

Antibody & Fc engineering

Antibody
anti-ROR1 (zilovertamab)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
Target KD (nM)
2
Dev code
Cirmtuzumab
Epitope / domain
ROR1 Frizzled / cysteine-rich domain
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
MC-vc-PAB (vedotin)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
Symmetry
Symmetric
DAR (mean)
4
DAR homogeneity
Heterogeneous
Plasma t½
4.0 d
Cleavage trigger
Cathepsin B (Val-Cit)
Release control
Conditional
Hydrophilicity mask
None
Formula
C28H40N6O7
Linker MW
572.663 Da
Linker TPSA
200.03 Ų
Linker xLogP
0.6769
ADCdb linker
LIN0SQEDQ
In-vitro stability
-
Stability note
Inherited from MC-vc-PAB conventional Cys class. Wang NEJM Evidence 2022 PMID 38319241 Ph1 N=32 R/R MCL/CLL Q3W does not tabulate clinical t½ in d in open abstract; PK reportedly dose-proportional
05
Payload

Payload & physicochemistry

Payload profile
Payload
MMAE
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
MMAE (monomethyl auristatin E)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
Yes
PAMPA rank
1
MW
718 Da
XLogP3
4.1
logD₇.₄
2.7
TPSA
150 Ų
pKa
9.1 pKa
Charge pH 7.4
+1
H-bond donors
4
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C39H67N5O7
PubChem CID
11542188
ADCdb payload
PAY0FSXOW
Hydrophobicity · logD₇.₄
hydrophilic −2+2.7+4 lipophilic
Bioactivity note
No payload IC50 listed on ADCdb/PubChem pages. ADCdb reports clinical ORR ~30-60% (indication/line-dependent) and preclinical xenograft TGI ~0-100% correlating with ROR1 expression. MMAE is a potent antimitotic (tubulin inhibitor).
06
Dosing & regimen

Dosing

RP2D dose
2.5 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
32
Dose basis
TBW
Trial phase
Phase 2/3
Dose-OAE available
No
Tox summary basis
RP2D
08
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)
0
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
-
Surface subtype
None
Grading scale
CTCAE v5.0
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
1.09 %
Cornea (limbal)
3.42 %
Conjunctiva
4.09 %
RPE
-
Retina (HPA)
-
Cross-trial comparability · source-verified
Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ Not comparable: symptom-driven ascertainment + grading scale not documented
Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification
09
Identity & registry

Identifiers, registry & notes

ADC id
zilovertamab-vedotin
Approval status
Investigational
Approval year
-
UniProt
Q01973
ADCdb ADC
DRG0ZMZUD
ADCdb antibody
ANI0CQMLX
ADCdb target
TAR0LTTSS
Primary source
Wang ML NEJM Evidence 2022;1(1):EVIDoa2100001 (PMID 38319241)
Aliases & development codes
MK-2140; anti-ROR1-MMAE
Notes
ROR1 low cornea/conjunctiva expression; 0% OAE explicitly verified in Wang 2022 NEJM Evidence ('did not observe instances of ocular toxicities'). V3.1: first author corrected Byrd→Wang.