ADC TOXICITY ATLAS
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JBH-492

Discontinued
JBH492; anti-CCR7 DM4 ADC
Sponsor
Novartis
Indication
Relapsed/refractory non-Hodgkin lymphoma (B- and T-cell) and chronic lymphocytic leukemia
Target family
GPCR
RP2D dose
No formal RP2D established (trial terminated); doses tested 0.4-3.6 mg/kg Q3W IV (5 dose levels, 3-7 pts/level); antitumor responses at 2.4-3.6 mg/kg
Every 3 weeks (Q3W)RP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
56.3%
G3+
-
RP2D
sagittal schematic · -

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
-
Limbus
AE
-
Express.
-
Conjunctiva
AE
-
Express.
-
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
Dominant tissue
Ocular surface
Surface subtype
Mixed
Reversibility
-
Reported ocular events
Eye toxicity (aggregate ocular AE)56.3%
n=16
Blurred vision (vision blurred)44%
n=16
Dry eye (dry eye syndrome)20%
n=25
Punctate keratitis12%
Visual acuity reduced8%
Corneal epithelial microcysts4%
Scleritis4%
Conjunctival haemorrhage4%
Keratorhexis (corneal perforation/rupture)4%
Vision blurred (SERIOUS adverse event)-
G3+ 4%
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
Cleavable
3.8
DAR
Payload
Microtubule/tubulin polymerization inhibitor (anti-mitotic)
Linker structure
structure not applicable
Payload structureC38H54ClN3O10S
C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)C)\C)OC)(NC(=O)O2)O
03
Antibody

Antibody & Fc engineering

Antibody
Humanized Fc-silenced anti-CCR7 IgG1 monoclonal antibody (no INN assigned)
Isotype
IgG1
Origin
Humanized
Fc modifications
Fc-silenced
Glycoengineering
-
Effector silencing
Fc-silenced IgG1 (effector/FcgammaR function silenced; specific mutations not disclosed)
FcγR binding
Retained
C1q binding
Unknown
04
Linker & conjugation

Linker chemistry

Linker
-
Class
Cleavable
Cleavage
Cleavable
Attachment
Site-specific (other)
Conjugation
Site-specific
Symmetry
Site-specific (paired)
DAR (mean)
3.8
DAR homogeneity
-
Plasma t½
-
Cleavage trigger
-
Release control
Conditional
Hydrophilicity mask
-
Formula
-
Linker MW
-
Linker TPSA
-
Linker xLogP
-
ADCdb linker
-
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
DM4 (ravtansine; mertansine DM4)
Class
Maytansinoid
Mechanism
Microtubule/tubulin polymerization inhibitor (anti-mitotic)
Released catabolite
DM4 (maytansinoid); DM4 ADCs additionally generate the bystander-active lipophilic metabolite S-methyl-DM4 (catabolite inferred from DM4 class; JBH-492 linker chemistry undisclosed)
Mechanistic subtype
Tubulin-maytansinoid
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
780.4 Da
XLogP3
3.2
logD₇.₄
-
TPSA
157 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
3
H-bond acceptors
11
IC50 (HCEC)
-
Formula
C38H54ClN3O10S
PubChem CID
11686439
ADCdb payload
PAY0GTSVM
06
Dosing & regimen

Dosing

RP2D dose
No formal RP2D established (trial terminated); doses tested 0.4-3.6 mg/kg Q3W IV (5 dose levels, 3-7 pts/level); antitumor responses at 2.4-3.6 mg/kg
Schedule
Every 3 weeks (Q3W)
Route
IV
Fractionated
No
n at RP2D
16
Dose basis
TBW
Trial phase
Phase 1
Dose-OAE available
No
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
56.3 %
OAE grade 3+
-
OAE data status
reported
Severity (weighted)
-
Keratopathy
-
Conjunctival
-
Dry eye
20 %
Blurred vision
44 %
Dominant tissue
Ocular surface
Surface subtype
Mixed
Grading scale
CTCAE (unversioned)
Reversibility
-
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: CTCAE (unversioned)Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
jbh-492
Approval status
Discontinued
Approval year
-
UniProt
P32248
ADCdb ADC
DRG0WXNKG
ADCdb antibody
ANI0PZSCN
ADCdb target
TAR0ZYPEF
Primary source
AACR 2024 Abstract CT174 (Cancer Res 2024;84(7_Suppl):CT174)
Aliases & development codes
JBH492; anti-CCR7 DM4 ADC
Notes
JBH-492 (Novartis) = first-in-class anti-CCR7 ADC: humanized Fc-silenced IgG1 conjugated site-specifically to maytansinoid DM4 via a cleavable linker, DAR 3.8. Trial NCT04240704 (Phase 1/Ib, r/r CLL + NHL) is terminated/discontinued; no formal RP2D/MTD declared. DENOMINATOR CAVEAT (important): two analysis populations appear across sources and are tagged per-row. (1) N=16 treated/evaluable -> AACR 2024 CT174 TRAE table: eye toxicity any-grade 56.3%, blurred vision 44%, AST increased 50%, fatigue 44%, diarrhoea 43%, overall any-Grade-3 TRAE 12.5% (2/16), 1 DLT = G3 thrombocytopenia lasting 13 d. (2) N=25 enrolled -> PatSnap/Synapse aggregated profile: anaemia 32%, thrombocytopenia 28%, neutropenia 20%, dry eye 20%, SAE 24%, any-AE 92%. The 56.3%/44% ocular figures (the reason this ADC qualifies) are from the N=16 set; dry eye 20% and the haematology %s are from the N=25 aggregate. Cohort: 25 enrolled = 24 NHL (ATLL 3, CTCL 4, DLBCL 7, FL 1, MCL 1, MZL 2, PTCL 3, others 3) + 1 CLL; median age 69; mean exposure 13.5 wks. Efficacy: ORR 6/16 (37.5%; 1 CR, 5 PR); responses at 2.4-3.6 mg/kg. ADCdb cross-ref IDs: ADC DRG0WXNKG; Antibody ANI0PZSCN; Antigen TAR0ZYPEF; Payload PAY0GTSVM; Target PATR0CXRBX. ADCdb has NO linker entry (conjugate type/linker class/cleavage/attachment all listed undisclosed), so the adcdb{} linker physchem fields are correctly blank. Note slight tension: ADCdb lists conjugation as undisclosed, but the AACR CT174 and ASH 2022 abstracts both state 'site-specific' conjugation and a 'cleavable' linker (specific chemistry not disclosed; DM4 cleavable linkers are typically reducible disulfides such as SPDB/sulfo-SPDB, but this is NOT stated for JBH-492 so left unasserted). Payload DM4 physchem from PubChem CID 11686439 per DB convention: MW 780.4, XLogP3 3.2, TPSA 157, formal charge 0 (maytansinoids neutral at pH 7.4, no ionizable basic centre). ADCdb computes a different XLogP (5.0) by a different algorithm; PubChem value retained per convention. logD7.4 and pKa not available in PubChem/literature -> blank. DM4 is bystander-active (lipophilic S-methyl-DM4 metabolite), same payload class as mirvetuximab soravtansine. Ocular interpretation: dominant ocular PTs are blurred vision (visual) + dry eye (ocular surface); no conjunctivitis or explicit keratopathy/keratitis % reported -> ocular_surface_subtype = Mixed (DM4 off-target corneal mechanism likely). Ocular-specific Grade 3+ NOT separately reported -> oae_g3plus_pct left blank (not zero). Reversibility not explicitly stated for JBH-492, though ocular AEs were managed by dose reduction (DM4-class ocular toxicity is typically reversible). CTCAE version not stated (trial 2020-2024, likely v5.0) -> ctcae_version left blank. Not represented in toxicity_rows because no matching organ_system enum: fatigue 44% (N=16). Pulmonary, Neurologic-PN (peripheral neuropathy) and Infusion-reaction AEs were NOT reported in accessible sources -> intentionally omitted (blank = not in literature, not zero). Primary clinical/ocular evidence is conference-abstract grade (Tier D); composition/payload facts Tier C. AACR CT174, ASH 2022 (Blood) and the ADC Review/aacrjournals pages returned HTTP 403; clinical figures were obtained via WebSearch snippets of those abstracts plus the PatSnap/Synapse and ADC Review drug profiles.