Antibody Information

General Information of This Antibody
Antibody ID
ANI0XSOTX
Antibody Name
Hertuzumab
Organization
RemeGen, Ltd.
Indication
Breast cancer
Synonyms
Disitamab
   Click to Show/Hide
Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
  Antigen Info 
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLVQSGAEVKKPGATVKISCKVSGYTFTDYYIHWVQQAPGKGLEWMGRVNPDHGDSYY
NQKFKDKATITADKSTDTAYMELSSLRSEDTAVYFCARNYLFDHWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV
FSCSVMHEALHNHYTQKSLSLSPGK
    Click to Show/Hide
Heavy Chain Varible Domain
EVQLVQSGAEVKKPGATVKISCKVSGYTFTDYYIHWVQQAPGKGLEWMGRVNPDHGDSYY
NQKFKDKATITADKSTDTAYMELSSLRSEDTAVYFCARNYLFDHWGQGTLVTVSS
    Click to Show/Hide
Heavy Chain Constant Domain 1
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV
    Click to Show/Hide
Heavy Chain Constant Domain 2
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
    Click to Show/Hide
Heavy Chain Constant Domain 3
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
    Click to Show/Hide
Heavy Chain Hinge Region
EPKSCDKTHTCPPCP
    Click to Show/Hide
Heavy Chain CDR 1
GYTFTDYY
    Click to Show/Hide
Heavy Chain CDR 2
VNPDHGDS
    Click to Show/Hide
Heavy Chain CDR 3
ARNYLFDH
    Click to Show/Hide
Light Chain Sequence
DIQMTQSPSSVSASVGDRVTITCKASQDVGTAVAWYQQKPGKAPKLLIYWASIRHTGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCHQFATYTFGGGTKVEIKRTVAAPSVFIFPPSD
EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS
KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
    Click to Show/Hide
Light Chain Varible Domain
DIQMTQSPSSVSASVGDRVTITCKASQDVGTAVAWYQQKPGKAPKLLIYWASIRHTGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCHQFATYTFGGGTKVEIK
    Click to Show/Hide
Light Chain Constant Domain
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
    Click to Show/Hide
Light Chain CDR 1
QDVGTA
    Click to Show/Hide
Light Chain CDR 2
WAS
    Click to Show/Hide
Light Chain CDR 3
HQFATYT
    Click to Show/Hide
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Disitamab vedotin [Approved]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
24.80%
High HER2 expression (HER2+++; IHC 3+)
Patients Enrolled
Locally advanced or metastatic gastric cancer with HER2-overexpression.
Administration Dosage
2.50 mg/kg IV every 2 weeks.
Related Clinical Trial
NCT Number NCT04714190  Clinical Status Phase 3
Clinical Description
Randomized, controlled, multicenter phase 1/2 clinical study evaluating the efficacy and safety of RC48-ADC for the treatment of locally advanced or metastatic gastric cancer with HER2-overexpression.
Primary Endpoint
The ORR was 24.80% (95% confidence interval [CI]: 17.50%-33.30%).
Other Endpoint
The median PFS and OS were 4.10 months (95% CI: 3.70-4.90 months) and 7.90 months (95% CI: 6.70-9.90 months), respectively. The most frequently reported adverse events were decreased white blood cell count (53.60%), asthenia (53.60%), hair loss (53.60%), decreased neutrophil count (52.00%), anemia (49.60%), and increased aspartate aminotransferase level (43.20%). Serious adverse events (SAEs) occurred in 45 (36.00%) patients, and RC48-related SAEs were mainly decreased neutrophil count (3.20%). Seven patients had adverse events that led to death were not RC48-related.

   Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
24.80%
High HER2 expression (HER2+++; IHC 3+)
Patients Enrolled
HER2overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least secondline therapy.
Administration Dosage
2.50 mg/kg alone by intravenous infusion during 30-90 min (60 min is recommended) every two weeks.
Related Clinical Trial
NCT Number NCT03556345  Clinical Status Phase 2
Clinical Description
A multicenter, open label single arm, phase 2 study to evaluate the effect and safety of recombinant humanized anti-HER2 monoclonal antibody-mmae conjugate for injection in HER2 overexpressing local advanced or metastatic gastric cancer.
Primary Endpoint
The ORR was 24.80% (95% confidence interval [CI]: 17.50%-33.30%).
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
21.05% (all)
35.71% (HER2 IHC2+/FISH-)
20.00% (IHC2+/FISH+)
13.64% (IHC3+)
15.00% (in patients who were pretreated with HER2-targeted drugs)
Patients Enrolled
Patients with incurable, locally advanced or metastatic solid cancers were eligible for inclusion if their tumors showed HER2 protein overexpression by IHC (3+or 2+), regardless of whether FISH was positive or negative.
Administration Dosage
0.10 mg/kg, 0.50 mg/kg, 1.00 mg/kg, 1.50 mg/kg, 2.00 mg/kg, 2.50 mg/kg, 3.00 mg/kg, 3.50 mg/kg, and 4.00 mg/kg; Q3W; dose expansion proceeded at the dose of 2.00 mg/kg Q2W.
Related Clinical Trial
NCT Number NCT02881190  Clinical Status Phase 1
Clinical Description
A tolerance, safety and pharmacokinetic ascending dose phase 1 study of RC48-ADC administered intravenously to subjects with HER2-positive malignant in advanced malignant solid tumors.
Primary Endpoint
The MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D.
Other Endpoint
ORR and DCR were 21.05% (12/57) and 49.12% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+and IHC3+, with ORRs of 35.71% (5/14), 20.00% (2/10), and 13.64% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efcacy, with ORR of 15.00% (3/20) and DCR of 45.00% (9/20).

   Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
51.20%
Patients Enrolled
Advanced or metastatic urothelial cancer.
Related Clinical Trial
NCT Number NCT04264936  Clinical Status Phase 1
Clinical Description
A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.
Primary Endpoint
The overall confirmed ORR as assessed by the BIRC was 51.20% (95% CI: 35.50%, 66.70%).
Other Endpoint
For RC48-ADC at 2.00 mg/kg, The median PFS and OS were 6.90 months (95% CI: 5.60, 8.90) and 13.90 months (95% CI: 9.10, NE), respectively.
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR)
80.00% (1L previously untreated mUC pts)
75.00% (pts with liver mets)
100.00% (pts with HER2% (3+))
77.80% (HER2% (2+))
66.70% (HER2% (1+))
50.00% (HER2% (0))
97.10% (in pts with PD-L1 CPS1)
50.00% (in CPS < 1)
Patients Enrolled
HER2-positive and even negative patients (pts) with metastatic urothelial carcinoma (mUC).
Administration Dosage
1.50 or 2.00 mg/kg RC48-ADC + 3 mg/kg toripalimab with the traditional 3+3 escalation design. In the expansion cohort, patients received the recommended dose of RC48-ADC + toripalimab every 2 weeks. The primary endpoints were safety/tolerability and recommended RC48-ADC dose.
Related Clinical Trial
NCT Number NCT04264936  Clinical Status Phase 1
Clinical Description
A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.
Primary Endpoint
At data cutoff, confirmed investigator-assessed ORR=75.00% (95%CI: 50.90-91.30), including 15.00% CRs; DCR=95.00% (95%CI: 75.10-99.90).
Other Endpoint
The ORR for 1L previously untreated mUC pts was 80.00%. The ORR for pts with liver mets was 75.00%. The ORR was 100.00% for pts with HER2 (3+), 77.80% for HER2 (2+), 66.70% for HER2 (1+), and 50.00% for HER2 (0) respectively. The ORR was 97.10% in pts with PD-L1 CPS1 and 50.00% in CPS < 1.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 61.20% (Day 22) Moderate HER2 expression (HER2++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model6)
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 64.50% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model8)
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 70.80% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model9)
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.80% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model3)
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 89.60% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model5)
Experiment 6 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.00% (Day 22) High HER2 expression (HER2+++; IHC 3+)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model7)
Experiment 7 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model1)
Experiment 8 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 22) High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model2)
Experiment 9 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 22) Moderate HER2 expression (HER2++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model Gastric cancer PDX model (PDX: Model4)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
90.00 ng/mL
Low HER2 expression (HER2+; IHC 1+)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with PBS, ADC (5 mg/kg), PD-1 antibody (10 mg/kg), or their combination (ADC+PD-1 antibody or ADC+PD-L1 antibody) for 10 days.
In Vivo Model Triple-negative breast cancer cell line E0771-hHER2 xenograft model
In Vitro Model Mammary gland malignant neoplasms EO771 cells CVCL_GR23
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.80 ug/mL
High HER2 expression (HER2+++)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.30 ug/mL
High HER2 expression (HER2+++; IHC 3+)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model Gastric tubular adenocarcinoma SNU-216 cells CVCL_3946
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.80 ug/mL
Moderate HER2 expression (HER2++; IHC 2+)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model Gastric signet ring cell adenocarcinoma NUGC-4 cells CVCL_3082
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
52.40 ug/mL
Moderate HER2 expression (HER2++; IHC 2+)
Method Description
The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model Gastric carcinoma HGC-27 cells CVCL_1279
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.91 ng/mL
High HER2 expression (HER2+++)
Method Description
To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [7]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
11.28 ng/mL
High HER2 expression (HER2+++)
Method Description
To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC [7]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
14.54 ng/mL
High HER2 expression (HER2+++)
Method Description
To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
References
Ref 1 Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study. Cancer Commun (Lond). 2021 Nov;41(11):1173-1182.
Ref 2 Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Gastric Cancer. 2021 Jul;24(4):913-925.
Ref 3 A Open-label, Single-arm, Phase Ib/II Study of RC48-ADC and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer, NCT04264936
Ref 4 Preliminary results of RC48-ADC combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma. Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022) 515-515.
Ref 5 From AVATAR Mice to Patients: RC48-ADC Exerted Promising Efficacy in Advanced Gastric Cancer With HER2 Expression. Front Pharmacol. 2022 Jan 5;12:757994.
Ref 6 A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+tumors in hPD-1 transgenic mouse model and contributes immune memory formation. Breast Cancer Res Treat. 2022 Jan;191(1):51-61.
Ref 7 Proton pump inhibitors interfere with the anti-tumor potency of RC48ADC. Toxicol In Vitro. 2022 Mar;79:105292.

If you find any error in data or bug in web service, please kindly report it to Dr. Shen et al.