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Vorsetuzumab mafodotin Discontinued SGN-75; anti-CD70-MMAF
RP2D dose
3 mg/kg Q3W Q3W RP2D
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
57%
Hepatic
70%
Neutrop.
-
Thrombo.
26%
Anemia
-
GI
30%
ILD
-
Neuro.
11%
Also reported Other · 2 · 1 system
8 adverse-event terms
Ocular Toxicity Target expression Compare
sagittal schematic · Reversible
↳ Tissues shaded by reported adverse-event rate.
Off-target signature
15% corneal toxicity, yet the CD70 target is detected in only 0.82% of central cornea - toxicity is not explained by target expression.
Surface subtype
Corneal (off-target)
Reported ocular events
Ocular adverse events (any type, composite) 57%
Ocular adverse events (grade >=3, composite) -
Vision blurred - WEEKLY schedule 18%
Corneal epitheliopathy 15%
Per-trial detail
Adverse events by trial SGN-75 Phase 1 first-in-human (NCT01015911) — Q3Wk schedule · Phase 1 — 34 events, n=47 SGN-75 Phase 1 first-in-human (NCT01015911) — weekly schedule · Phase 1 — 34 events, n=11 SGN75-001 (NCT01015911) · Phase 1 — 8 events, n=47 SGN-75 Phase 1 (NCT01015911) · Phase 1 — 5 events, n=26 SGN-75 Phase 1 first-in-human (NCT01015911) — Q3Wk schedule · Phase 1 — 1 event, n=47 SGN-75 Phase 1 (NCT01015911) · Phase 1 — 1 event, n=47 SGN-75 Phase 1 first-in-human (NCT01015911) — weekly schedule · Phase 1 — 1 event, n=11 SGN-75 Phase 1 (NCT01015911) · Phase 1 — 1 event Unattributed cohort — 1 event Unattributed cohort — 1 event SGN-75 Phase 1 first-in-human (NCT01015911) — Q3Wk schedule Phase 1 0.3-4.5 mg/kg (all doses pooled; MTD 3 mg/kg, RCC expansion at 3 mg/kg) IV every 3 weeks (Q3Wk) n=47 CTCAE 4.0 B to verify
Tannir et al., Invest New Drugs 2014;32(6):1246-57 PMID 25142258
34 adverse-event terms · 11 systems · expand a system below
Gastrointestinal disorders
60% G3+ 11%
Corneal epithelium defect
15% G3+ 9%
02 Construct
Molecular anatomy Linker structure C10H13NO4
O=C(O)CCCCCN1C(=O)C=CC1=O copy
Payload structure C39H65N5O8
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)NC copy
03 Antibody
Antibody & Fc engineering Antibody
h1F6 (vorsetuzumab)
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
DAR homogeneity
Heterogeneous
Cleavage trigger
Non-cleavable
Release control
Unconditional
DAR distribution
DAR 2, 4, 6, 8 evaluated preclinically; DAR4
Stability note
Inherited from mc-MMAF class (depatux-m 10 d, AGS-16C3F 8.3 d, denintuzumab 14 d, belantamab 13 d). Tannir 2014 Phase 1 N=47 R/R RCC/NHL paper does not separately tabulate t½ in d in open figures; Ph1 trial closed before MTD reached
Mechanism
Tubulin inhibitor
Released catabolite
Cys-mcMMAF
Mechanistic subtype
Tubulin-auristatin
Hydrophobicity · logD₇.₄
hydrophilic −2 -1 +4 lipophilic
Bioactivity note
ADCdb payload page (PAY0QLDVX, MMAF) reports microtubule-inhibitor IC50 values: HT-29 10 nM; SK-BR-3 5.3 nM; Hep-G2 7 nM; BT474-M1 8.8 nM. MMAF is an antimitotic tubulin-polymerization inhibitor; its C-terminal phenylalanine carboxylate attenuates membrane permeability relative t
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: Symptom-driven reporting Scale: Unknown Denominator: RP2D ⚠ Not comparable: symptom-driven ascertainment + grading scale not documented
Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort
0.3 or 0.6 mg/kg (escalation terminated; no MTD reached)
IV Days 1,8,15 of 28-day cycle (weekly)
n=11 · SGN-75 Phase 1 first-in-human
3 mg/kg (MTD; cohort pooled 0.3-4.5 mg/kg Q3W)
Every 3 weeks (Q3W), IV
n=47 · SGN75-001
0.3-4.5 mg/kg (all doses pooled; MTD 3 mg/kg, RCC expansion at 3 mg/kg)
IV every 3 weeks (Q3Wk)
n=47 · SGN-75 Phase 1 first-in-human
0.3-4.5 mg/kg (all doses pooled; MTD 3 mg/kg, RCC expansion at 3 mg/kg)
IV every 3 weeks (Q3Wk)
n=47 · SGN-75 Phase 1 first-in-human
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
vorsetuzumab-mafodotin
Approval status
Discontinued
Primary source
Tannir Invest New Drugs 2014
Aliases & development codes
SGN-75; anti-CD70-MMAF
Notes
MMAF-driven OAE on eye-absent CD70 target. V3.1: n_rp2d 35→47 (Q3W cohort); G3+ OAE 23% (prev blank, per review PMC4677113); blurred vision 18→11% (Q3W; 18 was weekly). PMID corrected 25169121→25142258.