← Atlas
Depatuxizumab mafodotin Discontinued ABT-414; depatux-m
Indication
EGFR-amplified GBM
Target family
Receptor tyrosine kinase
RP2D dose
1.25 mg/kg Q2W RP2D
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
94%
Hepatic
40.5%
Neutrop.
7.1%
Thrombo.
61%
Anemia
29.8%
GI
14.3%
ILD
-
Neuro.
-
Also reported Other · 21 · 9 systems
12 adverse-event terms
Ocular Toxicity Target expression Compare
sagittal schematic · Mixed
↳ Tissues shaded by reported adverse-event rate.
Off-target signature
94% corneal toxicity, yet the EGFR target is detected in only 89.35% of central cornea - toxicity is not explained by target expression.
Surface subtype
Corneal (off-target)
Reported ocular events
Corneal epitheliopathy (composite) 94%
Corneal epitheliopathy (eye disorders, composite) 71.4%
Corneal epithelial microcysts 6.4%
Lacrimation increased 5.8%
Per-trial detail
Adverse events by trial INTELLANCE-1 (NCT02573324) · Phase 3 — 167 events, n=273 INTELLANCE-1 (NCT02573324) · Phase 3 — 151 events, n=285 INTELLANCE-1 (NCT02573324) · Phase 3 — 124 events, n=335 INTELLANCE-1 (NCT02573324) · Phase 3 — 123 events, n=342 INTELLANCE-2 / EORTC 1410 (NCT02343406) · Phase 2 — 116 events, n=88 INTELLANCE-2 / EORTC 1410 (NCT02343406) · Phase 2 — 107 events, n=84 INTELLANCE-2 / EORTC 1410 (NCT02343406) · Phase 2 — 86 events, n=6 INTELLANCE-2 / EORTC 1410 (NCT02343406) · Phase 2 — 78 events, n=56 UNITE (NCT03419403) · Phase 3b — 68 events, n=14 INTELLANCE-1 (NCT02573324) · Phase 3 — 53 events, n=6 UNITE (NCT03419403) · Phase 3b — 48 events, n=12 INTELLANCE-2 / EORTC 1410 (NCT02343406) · Phase 2 — 47 events, n=21 INTELLANCE-1 (NCT02573324) · Phase 3 — 42 events, n=6 M12-356 / INTELLANCE-3 Arm B (NCT01800695) · Phase 1 — 25 events, n=66 M12-356 / INTELLANCE-3 Arm C (NCT01800695) · Phase 1 — 21 events, n=60 Unattributed cohort — 21 events UNITE (NCT03419403) · Phase 3b — 18 events, n=12 M12-356 / INTELLANCE-3 Arm A (NCT01800695) · Phase 1 — 17 events, n=45 INTELLANCE-2/EORTC-1410 · Phase 2 — 15 events, n=88 M13-379 first-in-human (NCT01741727) · Phase 1 — 14 events, n=56 INTELLANCE-J (NCT02590263) 2L Depatux-M + TMZ arm · Phase 1/2 — 11 events, n=29 INTELLANCE-1 (NCT02573324) · Phase 3 — 10 events, n=323 INTELLANCE-1 (NCT02573324) · Phase 3 — 10 events, n=313 Real-world monocentric cohort (Italy, no NCT) · RWD (real-world, retrospective/compassionate) — 9 events, n=36 INTELLANCE-1 (NCT02573324) · Phase 3 — 8 events, n=326 Goss 2018 (solid tumors) · Phase 1 — 8 events, n=56 INTELLANCE-1 · Phase 3 — 6 events, n=323 INTELLANCE-1 (NCT02573324) · Phase 3 — 5 events, n=323 INTELLANCE-2 / EORTC 1410 · Phase 2 — 5 events, n=84 ABT-414 Ph1 monotherapy (recurrent GBM) · Phase 1 — 5 events, n=66 INTELLANCE-J (NCT02590263) 2L Depatux-M DE (monotherapy) arm · Phase 1/2 — 5 events, n=9 INTELLANCE-1 (NCT02573324) · Phase 3 — 4 events, n=326 van den Bent 2017 (M12-356 mono) · Phase 1 — 4 events, n=66 Parrozzani long-term ocular safety (Padova, no NCT) · RWD (prospective single-center ophthalmology) — 4 events, n=15 M12-356 (Gan, Arms B+C) · Phase 1 — 3 events, n=38 Parrozzani confocal-microscopy ocular study (Padova, no NCT) · RWD (prospective single-center ophthalmology) — 3 events, n=10 INTELLANCE-1 (NCT02573324) · Phase 3 — 3 events, n=5 UNITE (NCT03419403) · Phase 3b — 1 event, n=38 UNITE (NCT03419403) · Phase 3b — 1 event, n=14 Unattributed cohort — 1 event Unattributed cohort — 1 event Unattributed cohort — 1 event Unattributed cohort — 1 event INTELLANCE-1 (NCT02573324) Phase 3 Depatux-M 2.0 mg/kg IV Q2W + adjuvant TMZ Adjuvant TMZ; depatux-M Q2W n=273 CTCAE MedDRA 24.1 (CT.gov se B
CT.gov posted results NCT02573324 (serious AE; 1/273) NCT02573324
167 adverse-event terms · 20 systems · expand a system below
Peripheral sensory neuropathy
1.83%
Haemorrhage intracranial
1.1%
Cerebral haemorrhage
0.73%
Transient ischaemic attack
0.37%
Vasogenic cerebral oedema
0.37%
Central nervous system necrosis
0.37%
Cerebrovascular accident
0.37%
Depressed level of consciousness
0.37%
Focal dyscognitive seizures
0.37%
Generalised tonic-clonic seizure
0.37%
Intracranial pressure increased
0.37%
Nervous system disorder
0.37%
Neurological decompensation
0.37%
Peripheral motor neuropathy
0.37%
Corneal epithelial microcysts
4.03%
Lacrimation increased
1.1%
Ulcerative keratitis
0.73%
Eyelid function disorder
0.37%
Optic ischaemic neuropathy
0.37%
02 Construct
Molecular anatomy Linker structure C10H13NO4
O=C(O)CCCCCN1C(=O)C=CC1=O copy
Payload structure C52H83N7O13S
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 copy
03 Antibody
Antibody & Fc engineering Antibody
ABT-806 (depatuxizumab)
Epitope / domain
Conformational disulfide-bonded loop EGFR aa 287-302
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
DAR homogeneity
Heterogeneous
Cleavage trigger
Non-cleavable
Release control
Unconditional
Stability note
Harmonic mean terminal t½: depatux-m (intact ADC) ~10 d; total depatux ~12 d; cys-mafodotin (released payload) ~4 d (Goss Cancer 2018 advanced solid tumor Ph1). Linear PK; no target-mediated disposition
Mechanism
Tubulin inhibitor
Released catabolite
Cys-mcMMAF (Cys-mafodotin)
Mechanistic subtype
Tubulin-auristatin
Hydrophobicity · logD₇.₄
hydrophilic −2 -1 +4 lipophilic
Bioactivity note
ADCdb (DRG0PXQWR) reports IC50 range 10.00-35.00 ug/mL across mesothelioma cell lines and tumor growth inhibition of approximately 87.5% in the MSTO-211H xenograft model. The free payload MMAF/Cys-mcMMAF is a potent tubulin polymerization inhibitor (anti-microtubule auristatin).
08 Ocular & expression
Ocular profile & eye-tissue target expression Target profile → Surface subtype
Corneal (off-target)
Target expression in eye tissues (HCA detection · HPA bulk)
Cross-trial comparability · source-verified
Ascertainment: Systematic eye exams Scale: CTCAE v4 Denominator: RP2D
Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort
Depatux-M 1.0 mg/kg IV (RPTD)
Depatux-M Q2W + TMZ
n=29 · INTELLANCE-J
Depatux-M 1.25 mg/kg IV Q2W + TMZ
Depatux-M Q2W + TMZ
n=88 · INTELLANCE-2 / EORTC 1410
1.25 mg/kg (reduced to 1.0 mg/kg)
Q2W
n=84 · INTELLANCE-2 / EORTC 1410
Depatux-M 1.25 mg/kg IV Q2W
Depatux-M Q2W monotherapy
n=84 · INTELLANCE-2 / EORTC 1410
Depatux-M 0.5/1.0/1.25 mg/kg IV (dose-escalation)
Depatux-M Q2W monotherapy
n=9 · INTELLANCE-J
Depatux-M 1.25 mg/kg IV (RP2D)
Depatux-M Q2W monotherapy
n=66 · M12-356 / INTELLANCE-3 Arm B
1.25 mg/kg
Q2W (D1, D15 of 28-day cycle)
n=66 · ABT-414 Ph1 monotherapy (recurrent GBM)
Depatux-M 1.25 mg/kg IV (RP2D)
Depatux-M Q2W + temozolomide
n=60 · M12-356 / INTELLANCE-3 Arm C
2.0 mg/kg during RT, then 1.25 mg/kg
Q2W (D1, D15 of 28-day cycle)
n=323 · INTELLANCE-1
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
Standard steroids
n=14 · UNITE
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
RT+TMZ then adjuvant TMZ; depatux-M/placebo Q2W
n=323 · INTELLANCE-1
Depatux-M (ABT-414) up to RP2D 2.0 mg/kg IV
Depatux-M Q2W + RT + TMZ, then adjuvant TMZ
n=45 · M12-356 / INTELLANCE-3 Arm A
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
Q2W; ocular prophylaxis per arm
n=38 · UNITE
Open-label Depatux-M 2.0 mg/kg IV Q2W + adjuvant TMZ
Adjuvant TMZ; depatux-M Q2W
n=6 · INTELLANCE-1
Open-label Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
RT + concurrent TMZ; depatux-M Q2W
n=6 · INTELLANCE-1
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
Standard steroids + vasoconstrictor + cold compress
n=12 · UNITE
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
Enhanced steroids + vasoconstrictor + cold compress
n=12 · UNITE
Depatux-M 2.0 mg/kg IV Q2W + RT + TMZ
RT + concurrent TMZ; depatux-M Q2W
n=342 · INTELLANCE-1
Depatux-M 2.0 mg/kg IV Q2W + adjuvant TMZ
Adjuvant TMZ; depatux-M Q2W
n=273 · INTELLANCE-1
Depatux-M 0.5-4.0 mg/kg IV; MTD 3.0 mg/kg Q3W (process A) / RP2D varied
Q3W (and prolonged-infusion / alternate-schedule cohorts)
n=56 · M13-379 first-in-human
Depatux-M (per INTELLANCE-2 schedule)
Depatux-M Q2W + TMZ
n=36 · Real-world monocentric cohort (Italy, no NCT)
Placebo + RT + TMZ
RT+TMZ then adjuvant TMZ; depatux-M/placebo Q2W
n=313 · INTELLANCE-1
Depatux-M (pediatric)
Depatux-M Q2W
n=6 · INTELLANCE-2 / EORTC 1410
Lomustine (CCNU)
Per investigator
n=56 · INTELLANCE-2 / EORTC 1410
Placebo + RT + TMZ
RT + concurrent TMZ; placebo Q2W
n=335 · INTELLANCE-1
Placebo + adjuvant TMZ
Adjuvant TMZ; placebo Q2W
n=285 · INTELLANCE-1
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
depatuxizumab-mafodotin
Approval status
Discontinued
Primary source
Lassman INTELLANCE-1 Neuro-Oncol 2023; PMC9925712
Aliases & development codes
ABT-414; depatux-m
Notes
V3.1 MAJOR CORRECTION: G3+ OAE 27→60% per Lassman Neuro-Oncol 2023 INTELLANCE-1 direct quote ('Grade 3 CE 55%, grade 4 perforation/blindness 5%'). Prior 27% misattributed. Severity ratio now 0.638 (was 0.287).