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FS-1502 Investigational LCB14-0110; anti-HER2-β-glucuronide-MMAF
Sponsor
LegoChem/Foshan Health
Target family
Receptor tyrosine kinase
RP2D dose
2.3 mg/kg Q3W RP2D
01 Multi-organ toxicity
Fingerprint & organ drill-down Any-grade Grade 3+
Ocular
55.3%
Hepatic
66.7%
Neutrop.
-
Thrombo.
34%
Anemia
26.7%
GI
33.3%
ILD
3.3%
Neuro.
-
Also reported Other · 15 · 4 systems
6 adverse-event terms
Ocular Toxicity Target expression Compare
sagittal schematic · Reversible
↳ Tissues shaded by reported adverse-event rate.
Reported ocular events
Eye disorders (composite ocular TEAE) 55.3%
Per-trial detail
Adverse events by trial FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 24 events, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 24 events, n=89 NCT03944499 (Li Nat Commun 2024) · Phase 1/2 — 14 events, n=150 FS-1502 Ph1a/1b · Phase 1a/1b — 14 events, n=150 Unattributed cohort — 3 events FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 2 events, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 2 events, n=89 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=150 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=89 FS-1502 first-in-human Phase 1a/1b (NCT03944499) · Phase 1a/1b — 1 event, n=89 Unattributed cohort — 1 event FS-1502 first-in-human Phase 1a/1b (NCT03944499) Phase 1a/1b 0.1-3.5 mg/kg (all doses pooled) Q3W or Q4W (IV) n=150 CTCAE CTCAE v5.0 B to verify
Li Q et al, Nat Commun 2024;15:5158 PMID 38886347 / PMC11183070 / NCT03944499 / DOI 10.1038/s41467-024-48798-w
24 adverse-event terms · 1 system · expand a system below
Aspartate aminotransferase increased
66.7%
Hypokalaemia
51.3% G3+ 15.3%
Alanine aminotransferase increased
44%
Platelet count decreased
34% G3+ 8%
Blood lactate dehydrogenase increased
26%
Hypercholesterolaemia
20.7%
Gamma-glutamyltransferase increased
18.7% G3+ 2%
White blood cell count decreased
18%
Hypertriglyceridaemia
16.7%
Neutrophil count decreased
— G3+ 2.7%
Electrocardiogram QT prolonged
— G3+ 2.7%
02 Construct
Molecular anatomy Payload structure C39H65N5O8
CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC copy
03 Antibody
Antibody & Fc engineering Antibody
anti-HER2 (trastuzumab biosimilar)
Fc modifications
C-terminal CaaX motif for prenylation
Linker
β-glucuronide + PAB
Attachment
Site-specific (enzymatic/non-natural AA)
Conjugation
Site-specific chemoenzymatic: farnesyltransferase prenylation of C-terminal CaaX motif + oxime ligation of payload
Symmetry
Site-specific (paired)
DAR homogeneity
Homogeneous
Cleavage trigger
beta-glucuronidase
Release control
Conditional
Conjugation site
C-terminal CVIM
In-vitro stability
85.38%@7d/rat-plasma
Stability note
Median terminal t½ 2.4–4.8 d at C1 doses ≥1.0 mg/kg in Li Q Nat Commun 2024 Ph1a/b N=150; nonlinear at <1.0 mg/kg with shorter t½ 0.6–2.3 d; time-dependent CL (mean CL drops from 13.0 to 8.75 mL/d/kg from C1 to C3 at 2.3 mg/kg). Highly stable in plasma — low unconjugated MMAF (Park 2020 LCB14 chemistry: β-gluc-MMAF >80 d in rat plasma stability per Jeffrey 2006)
Mechanism
Tubulin inhibitor
Released catabolite
MMAF (free / unconjugated monomethyl auristatin F)
Mechanistic subtype
Tubulin-auristatin
Hydrophobicity · logD₇.₄
hydrophilic −2 +0.9 +4 lipophilic
08 Ocular & expression
Ocular profile & eye-tissue target expression Target profile → Target expression in eye tissues (HCA detection · HPA bulk)
Cross-trial comparability · source-verified
Ascertainment: Symptom-driven reporting Scale: CTCAE v5 Denominator: RP2D
Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort
0.1-3.5 mg/kg (all doses pooled)
Q3W or Q4W (IV)
n=150 · FS-1502 first-in-human Phase 1a/1b
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 Approval status
Investigational
Primary source
Li Q Nat Commun 2024 PMID 38886347
Aliases & development codes
LCB14-0110; anti-HER2-β-glucuronide-MMAF
Notes
Cleavable β-gluc linker releases FREE MMAF (zwitterion) vs belantamab Cys-mcMMAF (-1) → dramatically lower G3+ (2.7 vs 77)