구조모아 (StructureMoa)항암 chemical structure spider web
방문프로그램 상세에서 관심 등록 후 2개 이상 모으면 여기서 한 번에 비교할 수 있습니다.
표가 넓으면 좌우로 스크롤하세요. 핵심 비교 모드에서는 중요 항목만 표시됩니다.
| 항목 | zolbetuximab (Vyloy, IMAB362, zolbetuximab-clzb, claudiximab) Astellas·CLDN18.2 (claudin-18.2) 26 trials·t½ ~11 days | zanidatamab (Ziihera, ZW25, zanidatamab-hrii) Jazz Pharmaceuticals / Zymeworks·HER2 (biparatopic) 35 trials·t½ ~7 days | trastuzumab deruxtecan (Enhertu, T-DXd, DS-8201) Daiichi Sankyo / AstraZeneca·HER2 240 trials·t½ ADC ~5.8 days; total antibody ~6.1 days; released DXd ~2.7 days (5.4 mg/kg q3w) |
|---|---|---|---|
Overview Program | Vyloy (zolbetuximab) | Ziihera (zanidatamab) | Enhertu (trastuzumab deruxtecan) |
Overview Company | Astellas | Jazz Pharmaceuticals / Zymeworks | Daiichi Sankyo / AstraZeneca |
Overview Modality | ANTIBODY | ANTIBODY | ADC |
Overview Target | CLDN18.2 (claudin-18.2) | HER2 (biparatopic) | HER2 |
Overview Indication | CLDN18.2-positive HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma | First-line HER2-positive gastric, GEJ, or esophageal adenocarcinoma; previously treated HER2-positive biliary tract cancer | HER2+ breast cancer, HER2-low, gastric |
Overview Phase | APPROVED | APPROVED | APPROVED |
Overview Status | APPROVED | APPROVED | APPROVED |
Overview Content status | Curated Core | Curated Core | Curated Core |
Overview Data Confidence | Data Confidence · High | Data Confidence · High | Data Confidence · High |
Overview Development Signal | Development Signal · Established | Development Signal · Established | Development Signal · Established |
Overview Approval status | FDA approved | FDA approved | FDA approved |
Positioning Key differentiator | Exploits a tight-junction protein that only becomes accessible after malignant transformation, creating tumor selectivity without a novel modality. | 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). | High DAR (~8), bystander effect, HER2-low activity |
Positioning Known limitation | CLDN18.2 heterogeneity and loss under treatment pressure. | HER2 heterogeneity, PI3K pathway activation, and bypass RTK signaling. | HER2 antigen loss/downregulation, payload efflux, and dose-limiting ILD/pneumonitis leading to discontinuation. |
Positioning Development positioning | Only approved CLDN18.2 agent; CAR-T and ADC competitors are still in trials. | Challenges the ToGA trastuzumab-chemo backbone in 1L HER2+ GEA; still the only HER2 agent with a dedicated BTC indication. | Leading efficacy in HER2 ADC class |
Technology Payload | — | — | DXd (topo-I inhibitor) |
Technology Linker | — | — | Cleavable tetrapeptide |
MoA Mechanism | Binds CLDN18.2 on gastric tumor cells and kills them through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. | Simultaneous binding of two non-overlapping HER2 epitopes crosslinks adjacent receptors, causing receptor clustering, internalization, and degradation alongside ADCC and complement activity. | Fam-trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate: humanized anti-HER2 IgG1 linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable topoisomerase I inhibitor. After binding HER2 on tumor cells, the conjugate is internalized; lysosomal proteases cleave the linker and release DXd, causing DNA damage and apoptosis. Released DXd can exert a bystander effect in neighboring cells. |
MoA Biomarker | CLDN18.2 IHC with ≥75% of tumor cells at moderate-to-strong membranous staining. | 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+. | HER2 expression (IHC/ISH per indication); higher systemic exposure associated with greater ILD incidence (FDA label §12.2). |
PK/PD Half-life | ~11 days | ~7 days | ADC ~5.8 days; total antibody ~6.1 days; released DXd ~2.7 days (5.4 mg/kg q3w) |
PK/PD Species | — | Cynomolgus monkey, Human, OS and PFS in GEA, ORR and DOR in BTC | Minipig, Pig, Human, Tumor response (ORR, PFS), ILD incidence rises with exposure |
PK/PD Animal (cat.) | Human, In vitro | Human, NHP, In vitro | Human, In vitro |
PK/PD Experiment | pharmacokinetic | pd | Pharmacokinetic |
PK/PD Biodistribution | — | — | Systemic exposure with tumor-selective HER2-mediated uptake |
Toxicology Species | Mouse | Human | Cynomolgus monkey, NHP, Rat, Minipig, Pig, Hamster, Human |
Toxicology Animal (cat.) | — | — | NHP |
Toxicology Major finding | Nausea and vomiting are frequent and often infusion-related, requiring rate adjustment and antiemetics. Hypoalbuminemia, appetite loss, and hypersensitivity also occur. | Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class. | ILD-like lung findings at high exposure |
Toxicology CRS | N/A | N/A | Minimal |
Toxicology NOAEL | — | — | 10 mg/kg |
Clinical Safety signal | Nausea and vomiting are frequent and often infusion-related, requiring rate adjustment and antiemetics. Hypoalbuminemia, appetite loss, and hypersensitivity also occur. | Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class. | ILD-like lung findings at high exposure |
Clinical Selected reported efficacy | 48.1% | ORR 52% | ORR 79.7% |
Clinical Reported ORR | — | 52% | 79.7% |
Clinical Reported PFS | — | ~5.5 mo | NA |
Clinical Reported OS | — | 15.54 | NA |
Clinical Result source | SPOTLIGHT (NCT03504397) / GLOW (NCT03653507) | HERIZON-BTC-01 (NCT04466891) | ClinicalTrials.gov NCT03529110 |
Clinical Program phase | APPROVED | APPROVED | APPROVED |
Clinical Trial activity | No active/completed counts | No active/completed counts | No active/completed counts |
Clinical Trial ref | NCT03504397 | NCT04466891 | NCT03529110 |
Preclinical Animal (cat.) | Mouse, In vitro | Unknown | Human, Mouse, In vitro |
프로그램 상세에서 관심 등록 후 2개 이상 모으면 여기서 한 번에 비교할 수 있습니다.
표가 넓으면 좌우로 스크롤하세요. 핵심 비교 모드에서는 중요 항목만 표시됩니다.
| 항목 | zolbetuximab (Vyloy, IMAB362, zolbetuximab-clzb, claudiximab) Astellas·CLDN18.2 (claudin-18.2) 26 trials·t½ ~11 days | zanidatamab (Ziihera, ZW25, zanidatamab-hrii) Jazz Pharmaceuticals / Zymeworks·HER2 (biparatopic) 35 trials·t½ ~7 days | trastuzumab deruxtecan (Enhertu, T-DXd, DS-8201) Daiichi Sankyo / AstraZeneca·HER2 240 trials·t½ ADC ~5.8 days; total antibody ~6.1 days; released DXd ~2.7 days (5.4 mg/kg q3w) |
|---|---|---|---|
Overview Program | Vyloy (zolbetuximab) | Ziihera (zanidatamab) | Enhertu (trastuzumab deruxtecan) |
Overview Company | Astellas | Jazz Pharmaceuticals / Zymeworks | Daiichi Sankyo / AstraZeneca |
Overview Modality | ANTIBODY | ANTIBODY | ADC |
Overview Target | CLDN18.2 (claudin-18.2) | HER2 (biparatopic) | HER2 |
Overview Indication | CLDN18.2-positive HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma | First-line HER2-positive gastric, GEJ, or esophageal adenocarcinoma; previously treated HER2-positive biliary tract cancer | HER2+ breast cancer, HER2-low, gastric |
Overview Phase | APPROVED | APPROVED | APPROVED |
Overview Status | APPROVED | APPROVED | APPROVED |
Overview Content status | Curated Core | Curated Core | Curated Core |
Overview Data Confidence | Data Confidence · High | Data Confidence · High | Data Confidence · High |
Overview Development Signal | Development Signal · Established | Development Signal · Established | Development Signal · Established |
Overview Approval status | FDA approved | FDA approved | FDA approved |
Positioning Key differentiator | Exploits a tight-junction protein that only becomes accessible after malignant transformation, creating tumor selectivity without a novel modality. | 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). | High DAR (~8), bystander effect, HER2-low activity |
Positioning Known limitation | CLDN18.2 heterogeneity and loss under treatment pressure. | HER2 heterogeneity, PI3K pathway activation, and bypass RTK signaling. | HER2 antigen loss/downregulation, payload efflux, and dose-limiting ILD/pneumonitis leading to discontinuation. |
Positioning Development positioning | Only approved CLDN18.2 agent; CAR-T and ADC competitors are still in trials. | Challenges the ToGA trastuzumab-chemo backbone in 1L HER2+ GEA; still the only HER2 agent with a dedicated BTC indication. | Leading efficacy in HER2 ADC class |
Technology Payload | — | — | DXd (topo-I inhibitor) |
Technology Linker | — | — | Cleavable tetrapeptide |
MoA Mechanism | Binds CLDN18.2 on gastric tumor cells and kills them through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. | Simultaneous binding of two non-overlapping HER2 epitopes crosslinks adjacent receptors, causing receptor clustering, internalization, and degradation alongside ADCC and complement activity. | Fam-trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate: humanized anti-HER2 IgG1 linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable topoisomerase I inhibitor. After binding HER2 on tumor cells, the conjugate is internalized; lysosomal proteases cleave the linker and release DXd, causing DNA damage and apoptosis. Released DXd can exert a bystander effect in neighboring cells. |
MoA Biomarker | CLDN18.2 IHC with ≥75% of tumor cells at moderate-to-strong membranous staining. | 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+. | HER2 expression (IHC/ISH per indication); higher systemic exposure associated with greater ILD incidence (FDA label §12.2). |
PK/PD Half-life | ~11 days | ~7 days | ADC ~5.8 days; total antibody ~6.1 days; released DXd ~2.7 days (5.4 mg/kg q3w) |
PK/PD Species | — | Cynomolgus monkey, Human, OS and PFS in GEA, ORR and DOR in BTC | Minipig, Pig, Human, Tumor response (ORR, PFS), ILD incidence rises with exposure |
PK/PD Animal (cat.) | Human, In vitro | Human, NHP, In vitro | Human, In vitro |
PK/PD Experiment | pharmacokinetic | pd | Pharmacokinetic |
PK/PD Biodistribution | — | — | Systemic exposure with tumor-selective HER2-mediated uptake |
Toxicology Species | Mouse | Human | Cynomolgus monkey, NHP, Rat, Minipig, Pig, Hamster, Human |
Toxicology Animal (cat.) | — | — | NHP |
Toxicology Major finding | Nausea and vomiting are frequent and often infusion-related, requiring rate adjustment and antiemetics. Hypoalbuminemia, appetite loss, and hypersensitivity also occur. | Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class. | ILD-like lung findings at high exposure |
Toxicology CRS | N/A | N/A | Minimal |
Toxicology NOAEL | — | — | 10 mg/kg |
Clinical Safety signal | Nausea and vomiting are frequent and often infusion-related, requiring rate adjustment and antiemetics. Hypoalbuminemia, appetite loss, and hypersensitivity also occur. | Embryo-fetal toxicity warning. Diarrhea, infusion-related reactions, and left ventricular dysfunction require monitoring, as with the HER2 antibody class. | ILD-like lung findings at high exposure |
Clinical Selected reported efficacy | 48.1% | ORR 52% | ORR 79.7% |
Clinical Reported ORR | — | 52% | 79.7% |
Clinical Reported PFS | — | ~5.5 mo | NA |
Clinical Reported OS | — | 15.54 | NA |
Clinical Result source | SPOTLIGHT (NCT03504397) / GLOW (NCT03653507) | HERIZON-BTC-01 (NCT04466891) | ClinicalTrials.gov NCT03529110 |
Clinical Program phase | APPROVED | APPROVED | APPROVED |
Clinical Trial activity | No active/completed counts | No active/completed counts | No active/completed counts |
Clinical Trial ref | NCT03504397 | NCT04466891 | NCT03529110 |
Preclinical Animal (cat.) | Mouse, In vitro | Unknown | Human, Mouse, In vitro |
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