ADC TOXICITY ATLAS
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AGS-16C3F

Discontinued
CHO-produced successor of AGS-16M8F; anti-ENPP3-mcMMAF
Sponsor
Agensys/Astellas/Seagen
Indication
ENPP3+ RCC
Target family
Ectonucleotidase
RP2D dose
1.8 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
85%
G3+
21%
RP2D
sagittal schematic · Reversible
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
59%
Express.
2.79%
Limbus
AE
-
Express.
4.15%
Conjunctiva
AE
-
Express.
5.7%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
0.3 nTPM
Off-target signature

59% corneal toxicity, yet the ENPP3 (CD203c) target is detected in only 2.79% of central cornea - toxicity is not explained by target expression.

Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Reversibility
Reversible
Reported ocular events
Ocular toxicity (any ocular sign or symptom)85%
n=34
Keratopathy (corneal events; microcysts)59%
G3+ 21%n=34
Ocular toxicity (any postbaseline ocular diagnosis)44%
n=59
Vision blurred39%
G3+ 2%n=66
Keratitis32.4%
G3+ 17.6%n=34
Keratopathy20%
n=59
Eye pain10.61%
non-seriousn=66
Dry eye10%
G3+ 3%n=66
Photophobia7.58%
non-seriousn=66
Diplopia6.06%
non-seriousn=66
Cataract2%
Retinopathy2%
Keratopathy (corneal events) Grade 4-
Per-trial detail

Adverse events by trial

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell CarcinomaPHASE2real-worldn=66CTCAE NR (ClinicalTrials.govPooledC
ClinicalTrials.gov NCT02639182 posted results, adverse events module (non-serious; 19/131 pooled across arms)
116 adverse-event terms · 20 systems · expand a system below
GI18
Nausea
46.97%non-serious
31/66
Vomiting
27.27%non-serious
18/66
Constipation
24.24%non-serious
16/66
Abdominal pain
18.18%non-serious
12/66
Diarrhoea
18.18%non-serious
12/66
Dry mouth
9.09%non-serious
6/66
Abdominal distension
6.06%non-serious
4/66
Dyspepsia
6.06%non-serious
4/66
Stomatitis
3.03%non-serious
2/66
Dysphagia
3.03%non-serious
2/66
Gastrooesophageal reflux disease
1.52%non-serious
1/66
Abdominal hernia
0%serious
0/66
Abdominal pain upper
0%serious
0/66
Inguinal hernia
0%serious
0/66
Pancreatitis
0%serious
0/66
Pneumoperitoneum
0%serious
0/66
Small intestinal obstruction
0%serious
0/66
Oral pain
0%non-serious
0/66
Musculoskeletal13
General10
Pulmonary10
Neurologic (other)9
Metabolic7
Infections6
Investigations6
Dermatologic6
Injury5
Ocular5
Vision blurred
39.39%non-serious
26/66
Dry eye
21.21%non-serious
14/66
Eye pain
10.61%non-serious
7/66
Photophobia
7.58%non-serious
5/66
Diplopia
6.06%non-serious
4/66
Vascular5
Cardiac4
Psychiatric3
Hematologic2
Renal2
Other2
Endocrine1
Hepatic1
Neoplasms1
02
Construct

Molecular anatomy

Antibody
IgG2
Human
Linker
Non-cleavable
Non-cleavable
4
DAR
Payload
Cys-mcMMAF
Tubulin inhibitor
Linker structureC10H13NO4
O=C(O)CCCCCN1C(=O)C=CC1=O
Payload structureC52H83N7O13S
drag · scroll to zoom
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN3C(=O)CC(C3=O)SC[C@@H](C(=O)O)N
03
Antibody

Antibody & Fc engineering

Antibody
AGS-16 Ab (anti-ENPP3)
Isotype
IgG2
Origin
Human
Fc modifications
Noneinferred
Glycoengineering
Standardinferred
Effector silencing
None
FcγR binding
Retained
C1q binding
Reducedinferred
Target KD (nM)
0.25
Epitope / domain
ENPP3 extracellular domain
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
mc (non-cleavable)
Class
Non-cleavable
Cleavage
Non-cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
Symmetry
Symmetric
DAR (mean)
4
DAR homogeneity
Heterogeneous
Plasma t½
8.3 d
Cleavage trigger
Non-cleavable
Release control
Unconditional
Hydrophilicity mask
Noneinferred
Cell line
CHO
Formula
C10H13NO4
Linker MW
211.217 Da
Linker TPSA
74.68 Ų
Linker xLogP
0.5564
ADCdb linker
LIN0TAFAV
In-vitro stability
-
Stability note
Median t½ of total Ab after first dose 8.29 d (range 4.01–14.2) per Thompson CCR 2018 Ph1 N=58; cys-mcMMAF released payload t½ ~4 d. CHO-produced anti-ENPP3 IgG2; classical mc-MMAF chemistry
05
Payload

Payload & physicochemistry

Payload profile
Payload
Cys-mcMMAF
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
Cys-mcMMAF
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
No
PAMPA rank
6
MW
1046.3 Da
XLogP3
1.4
logD₇.₄
-1
TPSA
301 Ų
pKa
3.5 pKa
Charge pH 7.4
-1
H-bond donors
5
H-bond acceptors
15
IC50 (HCEC)
-
Formula
C52H83N7O13S
PubChem CID
86278355
ADCdb payload
PAY0QLDVX
Potency IC50 (nM)
0.12
Hydrophobicity · logD₇.₄
hydrophilic −2-1+4 lipophilic
Bioactivity note
Payload mechanism: MMAF is a microtubule (MT) inhibitor (ADCdb payload PAY0QLDVX therapeutic target 'Microtubule'). ADCdb cell-line cytotoxicity for the ADC: IC50 1.1 nM (ROSA KIT D816V), 2.73 nM (ROSA KIT D816V Gluc), 109.9 nM (HMC-1.1), 146.5 nM (HMC-1.2). Clinical: Phase 1 NCT
06
Dosing & regimen

Dosing

RP2D dose
1.8 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
34
Dose basis
TBW
Trial phase
Phase 2
Dose-OAE available
Yes
Tox summary basis
RP2D
ADA rate (%)
0 %
Target prevalence (%)
3 %contradicted
08
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
85 %
OAE grade 3+
21 %
OAE data status
reported
Severity (weighted)
40.2
Keratopathy
59 %
Conjunctival
-
Dry eye
50 %
Blurred vision
44 %
Dominant tissue
Cornea
Surface subtype
Corneal (off-target)
Grading scale
CTCAE v4.0
Reversibility
Reversible
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
2.79 %
Cornea (limbal)
4.15 %
Conjunctiva
5.7 %
RPE
-
Retina (HPA)
0.3 nTPM
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D
Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort
1.8 mg/kg (RP2D); AE table pooled across 0.6-4.8 mg/kg
Q3W IV
59%
n=34 · AGS-16C3F Phase 1 (Thompson 2018)
1.8 mg/kg
IV once every 3 weeks (q3w)
39.4%
n=66 · Randomized Phase 2 AGS-16C3F vs axitinib
1.8 mg/kg (RP2D)
Q3W IV
20%
n=66 · AGS-16C3F vs axitinib Phase 2
1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
7.7%
n=13 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8 mg/kg
2%
2.7 mg/kg
IV q3w (every 21 days), 60-min infusion
15.4%
n=13 · Phase 1 AGS-16C3F(CHO) monotherapy
3.6 mg/kg
IV q3w (every 21 days), 60-min infusion
50%
n=6 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
85%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
59%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
4.8 mg/kg
IV q3w (every 21 days), 60-min infusion
50%
n=2 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
32.4%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
26%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
21%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
17.6%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
1.8-4.8 mg/kg (pooled); RP2D 1.8 mg/kg
IV q3w (every 21 days), 60-min infusion
17.6%
n=34 · Phase 1 AGS-16C3F(CHO) monotherapy
—
39.39%
n=66 · A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
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
ags-16c3f
Approval status
Discontinued
Approval year
-
UniProt
O14638
ADCdb ADC
DRG0QRDUT
ADCdb antibody
ANI0JHLRK
ADCdb target
TAR0SJQDK
Primary source
Thompson CCR 2018 PMID 29848572no such source
Aliases & development codes
CHO-produced successor of AGS-16M8F; anti-ENPP3-mcMMAF
Notes
Monotonic dose-OAE escalation 0%→100% from 0.6→4.8 mg/kg (Thompson 2018). V3.1 FLAG: full dose-cohort AE table not accessible via open web; OAE rates 85%/29%/59% retained from v2 Thompson tables but need verification from full PDF. Ph2 RCC arm (Kollmannsberger 2021) shows lower keratopathy 22%.no such source