Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0RYBMQ
ADC Name
SHR-A1201
Synonyms
SHR A1201; SHR-A1201; SHRA1201
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Organization
Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.
Drug Status
Phase 1
Drug-to-Antibody Ratio
3.5
Structure
Antibody Name
Trastuzumab
  Antibody Info 
Antigen Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
  Antigen Info 
Payload Name
Mertansine DM1
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Succinimidyl-4- (N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
  Linker Info 
Conjugate Type
Random conjugation through nucleophilic lysines.
Combination Type
Emtansine
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 17 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Time to Maximum Concentration (Tmax) 1.5 h
The maximum plasma concentrations (Cmax) of the prototype drug SHR-A1201, total antibody trastuzumab and small molecule DM1 all occurred at 1.5 h
 [1]
Time to Maximum Concentration (Tmax) 1.5 h
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3).
 [1]
Maximum Observed Concentration (Cmax) 32739.2±7665.7 ng/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 1866.92±95.49 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 1885.62±94.70 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 1.58 h
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3).
 [1]
Maximum Observed Concentration (Cmax) 66124.1±8975.6 ng/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 5100.78±517.96 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 5139.04±523.88 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 1.5 h
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3).
 [1]
Maximum Observed Concentration (Cmax) 94826.2±17 634.0 ng/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 8427.95±1601.17 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 8566.14±1642.86 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 1.5 h
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3).
 [1]
Maximum Observed Concentration (Cmax) 123422.5±23 287.0 ng/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 10265.67±1569.02 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 10532.57±1527.22 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUCinf.
 [1]
Distribution
Click To Hide/Show 13 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Volume of Distribution (Vd) 4.28 L
In this study, the Vd of the SHR-A1201 prototype was 4.28 L.
 [1]
Area Under the Concentration-Time Curve (AUC) 1866.92±95.49 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 1885.62±94.70 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUCinf.
 [1]
Volume of Distribution (Vd) 2.32±0.45 L
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 5100.78±517.96 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 5139.04±523.88 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUCinf.
 [1]
Volume of Distribution (Vd) 2.61±0.34 L
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 8427.95±1601.17 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 8566.14±1642.86 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUCinf.
 [1]
Volume of Distribution (Vd) 3.20±0.12 L
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 10265.67±1569.02 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 10532.57±1527.22 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUCinf.
 [1]
Volume of Distribution (Vd) 4.28±0.58 L
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3).
 [1]
Metabolism
Click To Hide/Show 8 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1866.92±95.49 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 1885.62±94.70 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 5100.78±517.96 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 5139.04±523.88 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 8427.95±1601.17 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 8566.14±1642.86 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 10265.67±1569.02 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 10532.57±1527.22 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUCinf.
 [1]
Excretion
Click To Hide/Show 17 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Elimination Half-Life (t1/2) 96.1 h
In the 4.8 mg/kg dose group, and their average half-lives were 96.1 h (4 days)
 [1]
Area Under the Concentration-Time Curve (AUC) 1866.92±95.49 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 1885.62±94.70 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3), AUCinf.
 [1]
Elimination Half-Life (t1/2) 38.42±3.61 h
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3).
 [1]
Clearance (CL) 0.04±0.00 L/h
Pharmacokinetic parameters of SHR-A1201, 1.2 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 5100.78±517.96 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 5139.04±523.88 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3), AUCinf.
 [1]
Elimination Half-Life (t1/2) 61.48±10.79 h
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3).
 [1]
Clearance (CL) 0.03±0.01 L/h
Pharmacokinetic parameters of SHR-A1201, 2.4 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 8427.95±1601.17 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 8566.14±1642.86 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3), AUCinf.
 [1]
Elimination Half-Life (t1/2) 79.81±9.99 h
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3).
 [1]
Clearance (CL) 0.03±0.00 L/h
Pharmacokinetic parameters of SHR-A1201, 3.6 mg/kg (N=3).
 [1]
Area Under the Concentration-Time Curve (AUC) 10265.67±1569.02 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 10532.57±1527.22 ug*h/mL
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3), AUCinf.
 [1]
Elimination Half-Life (t1/2) 96.1±11.83 h
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3).
 [1]
Clearance (CL) 0.03±0.00 L/h
Pharmacokinetic parameters of SHR-A1201, 4.8 mg/kg (N=3).
 [1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  CTR20191558
PHASE1
Undisclosed
Undisclosed  Undisclosed
Phase 1
This phase 1 study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase 1 study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.20 mg/kg, 2.40 mg/kg, 3.60 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201.

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Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Related Clinical Trial
NCT Number CTR20191558  Clinical Status PHASE1
Clinical Description .
Experiment 2 Reporting the Activity Date of This ADC [2]
Patients Enrolled
HER2-positive locally advanced or metastatic breast cancer (positivity for HER2 was defined as a score of 2+ in immunohistochemical analysis and a positive result in fluorescence in situ hybridization or a score of 3+ in immunohistochemical analysis), the standard treatment was invalid or there was no effective standard treatment plan, the Eastern Cooperative Oncology Group performance status score was 0-1.

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Administration Dosage
4 dose-escalation sequences, 1.20 mg/kg, 2.40 mg/kg, 3.60 mg/kg and 4.80 mg/kg, once every 21days, as a 90-min intravenous infusion.
References
Ref 1 Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study
Ref 2 Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study. Anticancer Drugs. 2023 Jul 1;34(6):763-774.