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SC-011 / ABBV-011 (SC17, SEZ6, calicheamicin) Discontinued SC-011; SC011; ABBV011; ABBV 011
Sponsor
AbbVie (originated Stemcentrx)
Indication
Relapsed/refractory small cell lung cancer (SCLC)
RP2D dose
1.0 mg/kg Every 3 weeks (Q3W) RP2D
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
0%
Hepatic
35%
Neutrop.
-
Thrombo.
40%
Anemia
15%
GI
45%
ILD
-
Neuro.
-
Also reported Other · 11 · 2 systems
1 adverse-event term
Ocular Toxicity Target expression Compare
sagittal schematic · No ocular or neurologic toxicities reported
↳ Tissues shaded by reported adverse-event rate.
Reversibility
No ocular or neurologic toxicities reported
Reported ocular events
Any eye toxicity (explicitly assessed, none reported) 0%
Per-trial detail
Adverse events by trial ABBV-011 FIH Phase I (NCT03639194 / M17-327) · Phase 1 — 36 events, n=99 ABBV-011 FIH Phase I (NCT03639194 / M17-327) · Phase 1 — 36 events, n=40 ABBV-011 Ph1 (NCT03639194) · Phase 1 — 20 events, n=99 ABBV-011 Ph1 (NCT03639194) · Phase 1 — 17 events, n=40 NCT03639194 · Phase 1 — 13 events, n=99 Unattributed cohort — 5 events NCT03639194 · Phase 1 — 2 events, n=40 Unattributed cohort — 2 events NCT03639194 · Phase 1 — 1 event, n=99 NCT03639194 (FIH Phase 1) · Phase 1 — 1 event, n=99 Unattributed cohort — 1 event ABBV-011 FIH Phase I (NCT03639194 / M17-327) Phase 1 0.3-2.0 mg/kg (pooled) IV Q3W (one cohort 0.5 mg/kg D1,8 Q3W) n=99 CTCAE 5.0 B to verify
Morgensztern et al., Clin Cancer Res 2024;30(22):5042-5052 PMID 39287821 | PMC11565168 | NCT03639194
36 adverse-event terms · 7 systems · expand a system below
Any treatment-related AE (TRAE)
77%
TEAE leading to dose interruption
34%
TRAE leading to dose interruption
29%
TEAE leading to treatment discontinuation
19%
TRAE leading to treatment discontinuation
13%
TEAE leading to dose reduction
8%
TRAE leading to dose reduction
8%
Dose-limiting toxicity (DLT)
1%
TEAE leading to death
— G5 19%
02 Construct
Molecular anatomy
Payload
DNA double-strand break induction (enediyne DNA-damaging agent)
Linker structure C26H45N3O11
NCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCC1C(=O)C=CC1=O copy
Payload structure C57H76IN3O22S4
CCN([C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\C#C[C@@]4(CC(=O)C(=C3C4=CCSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O)C(=O)C copy
03 Antibody
Antibody & Fc engineering Effector silencing
Not reported (IgG1 backbone; no explicit Fc-silencing described)
Epitope / domain
SEZ6 extracellular domains N1, N3, SD1, SD4
Linker
LD19.10 (Mc-PEG8 hindered-disulfide linker)
Attachment
Site-specific (engineered Cys)
Conjugation
Site-specific cysteine conjugation
Symmetry
Site-specific (paired)
DAR homogeneity
Homogeneous
Cleavage trigger
Non-cleavable; payload released via reduction of hindered disulfide (LD19.10), before or after antibody catabolism
Hydrophilicity mask
Discrete-PEG-spacer
Platform
AbbVie/Stemcentrx site-specific cysteine-engineered ADC platform
Conjugation site
Two engineered cysteines
Stability note
LD19.10 lacks the acid-labile dimethylhydrazide
Payload
N-acetyl-gamma-calicheamicin
Mechanism
DNA double-strand break induction (enediyne DNA-damaging agent)
Released catabolite
N-acetyl-gamma-calicheamicin (active enediyne warhead)
Mechanistic subtype
DNA-strand-break
Bioactivity note
ADCdb payload page (PAY0GKVJX) reports payload potency IC50 = 112 pmol/L (0.112 nM) in HEK-293T cells. Payload mechanism: enediyne that, after trisulfide reduction/Bergman-type cyclization, generates a diradical inducing DNA double-strand breaks.
Schedule
Every 3 weeks (Q3W)
08 Ocular & expression
Ocular profile & eye-tissue target expression Target profile → OAE data status
documented-absent
Reversibility
No ocular or neurologic toxicities reported
Target expression in eye tissues (HCA detection · HPA bulk)
Cross-trial comparability
Ascertainment: Symptom-driven reporting Scale: CTCAE v5 Denominator: RP2D ⚠ Not comparable: symptom-driven ascertainment
Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification 09 Identity & registry
Identifiers, registry & notes Approval status
Discontinued
Primary source
Morgensztern et al., Clin Cancer Res 2024;30(22):5042 (PMC11565168)
Aliases & development codes
SC-011; SC011; ABBV011; ABBV 011
Notes
SEZ6-targeting calicheamicin ADC for R/R SCLC; Phase 1 program terminated. Ocular finding is an explicit documented zero: "no eye toxicities of any grade related to ABBV-011 treatment were reported" and "no on-target neurologic or ocular toxicities" (Morgensztern et al. CCR 2024; CTCAE v5.0). Useful low/control case. NOTE on linker cleavage: ADCdb names the linker "Mc-PEG8-acid-labile linker" (LIN0KQAXA), but the primary literature (Mol Cancer Ther 2022, PMC9381089; clinical CCR 2024) describes the linker drug as LD19.10, a NON-cleavable linker that releases payload only upon reduction of a hindered disulfide (before/after antibody degradation), with maleimide (Mc) attachment and a PEG8 spacer. I report cleavage as non-cleavable per primary lit. NOTE on conjugation: ADCdb lists "Random Cysteines," but primary lit (PMC9381089) states site-specific cysteine conjugation at DAR=2 on a cysteine-engineered humanized IgG1 (SC17); I report site-specific cysteine, DAR 2. Linker physchem values (SMILES/formula/MW/TPSA/xLogP) are ADCdb's for the Mc-PEG8 linker fragment.