ADC TOXICITY ATLAS
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Pinatuzumab vedotin

Investigational
DCDT2980S; anti-CD22-MMAE
Sponsor
Genentech
Indication
CD22+ NHL
Target family
Siglec
RP2D dose
2.4 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
9.5%
G3+
0%
RP2D
sagittal schematic · Partial

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
0.5%
Limbus
AE
-
Express.
1.1%
Conjunctiva
AE
-
Express.
1.64%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
1.16%
0 nTPM
Dominant tissue
Peripheral nervous system / bone marrow
Surface subtype
None
Reversibility
Partial
Reported ocular events
Vision blurred9.5%
Dry eye3.2%
Visual impairment1.6%
Eye pain1.6%
Per-trial detail

Adverse events by trial

ROMULUS (pinatuzumab+rituximab arm)Phase 2pinatuzumab vedotin 2.4 mg/kg + rituximab 375 mg/m2 q21d (pina/rituximab IV)n=63CTCAE NRCto verify
CT.gov NCT01691898 all-cause mortality (derived G5; includes non-AE/PD deaths; crossover-inclusive) NCT01691898
139 adverse-event terms · 19 systems · expand a system below
GI19
Diarrhoea
44.4%
28/63
Nausea
31.7%
20/63
Constipation
28.6%
18/63
Abdominal pain
17.5%G3+ 1.6%
11/63
Vomiting
17.5%
11/63
Dry mouth
7.9%
5/63
Dyspepsia
6.3%
4/63
Gastrooesophageal reflux disease
6.3%
4/63
Abdominal discomfort
3.2%
2/63
Abdominal pain lower
3.2%
2/63
Haemorrhoids
3.2%
2/63
Colonic fistula
G3+ 1.6%
Duodenal perforation
G3+ 1.6%
Gastrointestinal haemorrhage
G3+ 1.6%
Upper gastrointestinal haemorrhage
G3+ 1.6%
Abdominal distension
1.6%
1/63
Abdominal pain upper
1.6%
1/63
Dysphagia
1.6%
1/63
Gastrointestinal pain
1.6%
1/63
Infections17
General13
Pulmonary12
Neurologic (other)11
Musculoskeletal10
Metabolic9
Dermatologic8
Investigations7
Hematologic5
Cardiac5
Injury5
Ocular4
Vision blurred
9.5%
6/63
Dry eye
3.2%
2/63
Eye pain
1.6%
1/63
Visual impairment
1.6%
1/63
Renal4
Psychiatric3
Ear2
Neoplasms2
Vascular2
Overall/Summary1
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
3.5
DAR
Payload
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-CD22 (pinatuzumab)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
Target KD (nM)
1.7
Epitope / domain
Binds CD22 epitope non-overlapping with epratuzumab
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)
3.5
DAR homogeneity
Heterogeneous
Plasma t½
8.18 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. Advani CCR 2017 PMID 27601593 Ph1 N=75 R/R B-NHL Q3W: dose-proportional PK, no numeric clinical t½ in d in open-access tables
05
Payload

Payload & physicochemistry

Payload profile
Payload
MMAE
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
MMAE (unconjugated 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
ADCdb lists the MMAE payload's mechanistic target as Microtubule (MT); MMAE is a potent antimitotic tubulin-polymerization inhibitor. No numeric IC50 reported on the ADCdb ADC page or the PubChem MMAE record.
06
Dosing & regimen

Dosing

RP2D dose
2.4 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
39
Dose basis
TBW
Trial phase
Phase 2
Dose-OAE available
No
Tox summary basis
RP2D
ADA rate (%)
1.4 %
Total-Ab t½ (d)
11.6
08
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
9.5 %
OAE grade 3+
0 %
OAE data status
reported
Severity (weighted)
2.9
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
Peripheral nervous system / bone marrow
Surface subtype
None
Grading scale
CTCAE v4.0
Reversibility
Partial
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
0.5 %
Cornea (limbal)
1.1 %
Conjunctiva
1.64 %
RPE
1.16 %
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 · ocular AE (any-grade) by cohort
pinatuzumab vedotin 2.4 mg/kg + rituximab 375 mg/m2
q21d (pina/rituximab IV)
9.5%
n=63 · ROMULUS (pinatuzumab+rituximab arm)
2.4 mg/kg
9.5%
3.2%
1.6%
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
09
Identity & registry

Identifiers, registry & notes

ADC id
pinatuzumab-vedotin
Approval status
Investigational
Approval year
-
UniProt
P20273
ADCdb ADC
DRG0PFKFR
ADCdb antibody
ANI0IESDV
ADCdb target
TAR0XTCGM
Primary source
Advani CCR 2017 PMID 27601593
Aliases & development codes
DCDT2980S; anti-CD22-MMAE
Notes
CD22 absent from cornea; 0% OAE verified in Advani 2017 CCR. V3.1: confirmed — paper has no ocular AEs; dominant toxicities are neutropenia and peripheral neuropathy.