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항목
AntibodyCurated CoreFDAApproved
zanidatamab (Ziihera, ZW25, zanidatamab-hrii)
Jazz Pharmaceuticals / Zymeworks·HER2 (biparatopic)
35 trials·t½ ~7 days
Overview
Program
Ziihera (zanidatamab)
Overview
Company
Jazz Pharmaceuticals / Zymeworks
Overview
Modality
ANTIBODY
Overview
Target
HER2 (biparatopic)
Overview
Indication
First-line HER2-positive gastric, GEJ, or esophageal adenocarcinoma; previously treated HER2-positive biliary tract cancer
Overview
Phase
APPROVED
Overview
Status
APPROVED
Overview
Content status
Curated Core
Overview
Data Confidence
Data Confidence · High
Overview
Development Signal
Development Signal · Established
Overview
Approval status
FDA approved
Positioning
Key differentiator
Dual-epitope binding drives receptor clustering, faster internalization, and stronger signaling blockade than either monoclonal alone. In GEA the label splits IHC 3+ (chemo doublet) from IHC 3+ or 2+/ISH+ (chemo + Tevimbra).
Positioning
Known limitation
HER2 heterogeneity, PI3K pathway activation, and bypass RTK signaling.
Positioning
Development positioning
Challenges the ToGA trastuzumab-chemo backbone in 1L HER2+ GEA; still the only HER2 agent with a dedicated BTC indication.
MoA
Mechanism
Simultaneous binding of two non-overlapping HER2 epitopes crosslinks adjacent receptors, causing receptor clustering, internalization, and degradation alongside ADCC and complement activity.
MoA
Biomarker
GEA: PATHWAY 4B5 IHC and VENTANA Dual ISH. IHC 3+ for chemo doublet; IHC 3+ or IHC 2+/ISH+ when Tevimbra is added. BTC: HER2 IHC 3+.
PK/PD
Half-life
~7 days
PK/PD
Species
Cynomolgus monkey, Human, OS and PFS in GEA, ORR and DOR in BTC
PK/PD
Animal (cat.)
Human, NHP, In vitro
PK/PD
Experiment
pd
Toxicology
Species
Human
Toxicology
Major finding
Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class.
Toxicology
CRS
N/A
Clinical
Safety signal
Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class.
Clinical
Selected reported efficacy
ORR 52%
Clinical
Reported ORR
52%
Clinical
Reported PFS
~5.5 mo
Clinical
Reported OS
15.54
Clinical
Result source
HERIZON-BTC-01 (NCT04466891)
Clinical
Program phase
APPROVED
Clinical
Trial activity
No active/completed counts
Clinical
Trial ref
NCT04466891
Preclinical
Animal (cat.)
Unknown