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; SHR-A1403; SHR-A1403, HTI-1066; SHRA1403
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Organization
Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.
Drug Status
Phase 1 (Terminated)
Indication
In total 1 Indication(s)
Solid tumor
Phase 1
Clinical Trial
Drug-to-Antibody Ratio
2
Structure
Antibody Name
A humanised anti-c-MET IgG2 monoclonal antibody
  Antibody Info 
Antigen Name
Hepatocyte growth factor receptor (MET)
  Antigen Info 
Payload Name
SHR152852
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
L2-MC
  Linker Info 
Conjugate Type
Undisclosed
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.