Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0OAWRK
ADC Name
SHR-A1403
Synonyms
HTI 1066; HTI-1066; SHR A1403; SHRA1403
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Organization
Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.
Drug Status
Phase 1
Indication
In total 1 Indication(s)
Solid tumors [ICD11:2A00-2A0Z|2B50-2F9Z]
Phase 1
Drug-to-Antibody Ratio
2
Antibody Name
SHR-A1403 mAb
  Antibody Info 
Antigen Name
Hepatocyte growth factor receptor (MET)
  Antigen Info 
Payload Name
SHR152852
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Uncleavable linker
  Linker Info 
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT03856541
Phase 1
A phase 1, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of SHR-a1403 with intravenous infusion in patients with advanced solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 95.5
%
Hepatic cancer PDX model (PDX: HCC)
Tumor Growth Inhibition value (TGI) 
≈ 98.3
%
Hepatic cancer PDX model (PDX: HCC)
Tumor Growth Inhibition value (TGI) 
≈ 98.5
%
Hepatic cancer PDX model (PDX: HCC)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 11 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 0
%
HCC827 cells (Afatinib resistant
HA1)
Lung adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 34.5
%
HCCLM3 cells
Adult hepatocellular carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 41.8
%
Lung cancer cells
Lung cancer
Tumor Growth Inhibition value (TGI) 
≈ 42.8
%
Gastric cancer cells
Gastric cancer
Tumor Growth Inhibition value (TGI) 
≈ 59.3
%
Lung cancer cells
Lung cancer
Tumor Growth Inhibition value (TGI) 
≈ 83.3
%
HCCLM3 cells
Adult hepatocellular carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 84.6
%
MKN45 cells
Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 89.9
%
MKN45 cells
Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 91.6
%
NCI-H1993 cells
Lung adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 92.8
%
HCC827 cells
Lung adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 98.8
%
HCCLM3 cells
Adult hepatocellular carcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 16 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
3.2
ng/mL
HCCLM3 cells
Adult hepatocellular carcinoma
Half Maximal Inhibitory Concentration (IC50) 
7.8
ng/mL
MKN45 cells
Gastric adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
11.8
ng/mL
HCC827 cells (Afatinib resistant
HA1)
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
16.3
ng/mL
NCI-H1993 cells
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
17.8
ng/mL
HCC827 cells (Gefitinib resistant)
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
26.6
ng/mL
HCC827 cells (Gefitinib resistant)
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
46.7
ng/mL
NCI-H441 cells
Lung papillary adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
53.9
ng/mL
Hs 578T cells
Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50) 
78.2
ng/mL
PC-3 cells
Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50) 
99.4
ng/mL
HCC827 cells (Gefitinib resistant)
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
130.8
ng/mL
HCC827 cells (Gefitinib resistant)
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
214.8
ng/mL
Caki-1 cells
Clear cell renal cell carcinoma
Half Maximal Inhibitory Concentration (IC50) 
918.9
ng/mL
HCC827 cells
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
1987.5
ng/mL
A-549 cells
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 10
ug/mL
NCI-N87 cells
Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 30
ug/mL
HCC827 cells (Afatinib resistant
HA2)
Lung adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Related Clinical Trial
NCT Number NCT03856541  Clinical Status Phase 1
Clinical Description A phase 1, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of SHR-a1403 with intravenous infusion in patients with advanced solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.50% (Day 17) High MET expression (MET+++)
Method Description
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (1 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model Hepatic cancer PDX model (PDX: HCC)
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.30% (Day 17) High MET expression (MET+++)
Method Description
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (3 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model Hepatic cancer PDX model (PDX: HCC)
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.50% (Day 17) High MET expression (MET+++)
Method Description
HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (10 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model Hepatic cancer PDX model (PDX: HCC)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 11 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 16) Negative MET expression (MET-)
Method Description
Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.

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In Vivo Model Non-small cell lung cancer HCC827 CDX model (CDX: HA1; Afatinib resistant)
In Vitro Model Lung adenocarcinoma HCC827 cells (Afatinib resistant; HA1) CVCL_2063
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 34.50% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.

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In Vivo Model Hepatic cancer CDX model
In Vitro Model Adult hepatocellular carcinoma HCCLM3 cells CVCL_6832
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 41.80% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 4 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.80% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.

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In Vivo Model Gastric cancer CDX model
In Vitro Model Gastric cancer Gastric cancer cells Homo sapiens
Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.30% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 6 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.30% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.

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In Vivo Model Hepatic cancer CDX model
In Vitro Model Adult hepatocellular carcinoma HCCLM3 cells CVCL_6832
Experiment 7 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84.60% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.

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In Vivo Model Gastric cancer CDX model
In Vitro Model Gastric adenocarcinoma MKN45 cells CVCL_0434
Experiment 8 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 89.90% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.

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In Vivo Model Gastric cancer CDX model
In Vitro Model Gastric adenocarcinoma MKN45 cells CVCL_0434
Experiment 9 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.60% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma NCI-H1993 cells CVCL_1512
Experiment 10 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.80% (Day 21) High MET expression (MET+++)
Method Description
Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.

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In Vivo Model Non-small cell lung cancer CDX model
In Vitro Model Lung adenocarcinoma HCC827 cells CVCL_2063
Experiment 11 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.80% (Day 21) High MET expression (MET+++)
Method Description
SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.

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In Vivo Model Hepatic cancer CDX model
In Vitro Model Adult hepatocellular carcinoma HCCLM3 cells CVCL_6832
Revealed Based on the Cell Line Data
Click To Hide/Show 16 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 3.20 ng/mL High MET expression (MET+++; IHC 3+)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Adult hepatocellular carcinoma HCCLM3 cells CVCL_6832
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 7.80 ng/mL Negative MET expression (MET-)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Gastric adenocarcinoma MKN45 cells CVCL_0434
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 11.80 ng/mL Moderate MET expression (MET++)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Afatinib resistant; HA1) CVCL_2063
Experiment 4 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 16.30 ng/mL High MET expression (MET+++)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Lung adenocarcinoma NCI-H1993 cells CVCL_1512
Experiment 5 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 17.80 ng/mL High MET expression (MET+++)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Gefitinib resistant) CVCL_2063
Experiment 6 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 26.60 ng/mL Negative MET expression (MET-)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Gefitinib resistant) CVCL_2063
Experiment 7 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 46.70 ng/mL Moderate MET expression (MET++)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Lung papillary adenocarcinoma NCI-H441 cells CVCL_1561
Experiment 8 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 53.90 ng/mL High MET expression (MET+++; IHC 3+)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Invasive breast carcinoma Hs 578T cells CVCL_0332
Experiment 9 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 78.20 ng/mL High MET expression (MET+++)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 10 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 99.40 ng/mL Moderate MET expression (MET++)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Gefitinib resistant) CVCL_2063
Experiment 11 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 130.80 ng/mL High MET expression (MET+++)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Gefitinib resistant) CVCL_2063
Experiment 12 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 214.80 ng/mL Moderate MET expression (MET++)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Clear cell renal cell carcinoma Caki-1 cells CVCL_0234
Experiment 13 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 918.90 ng/mL Moderate MET expression (MET++)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells CVCL_2063
Experiment 14 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1987.50 ng/mL High MET expression (MET+++; IHC 3+)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 15 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 ug/mL High MET expression (MET+++)
Method Description
The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 16 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 30.00 ug/mL Negative MET expression (MET-)
Method Description
To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).

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In Vitro Model Lung adenocarcinoma HCC827 cells (Afatinib resistant; HA2) CVCL_2063
References
Ref 1 A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR-A1403 With Intravenous Infusion in Patients With Advanced Solid Tumors
Ref 2 SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models. Acta Pharmacol Sin. 2019 Jul;40(7):971-979.
Ref 3 SHR-A1403, a novel c-mesenchymal-epithelial transition factor (c-Met) antibody-drug conjugate, overcomes AZD9291 resistance in non-small cell lung cancer cells overexpressing c-Met. Cancer Sci. 2019 Nov;110(11):3584-3594.

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