Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0LUQSH
ADC Name
RG7861
Synonyms
RG7861; DSTA4637S; Sym009
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Organization
Symphogen (Originator);Seagen (Top20 MNC);Genentech (Top20 MNC)
Drug Status
Phase 1 (discontinued)
Drug-to-Antibody Ratio
2
Structure
Antibody Name
MSTA3852A
  Antibody Info 
Antigen Name
Staphylococcus aureus bacteria
  Antigen Info 
Payload Name
dmDNA31
  Payload Info 
Therapeutic Target
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)
  Target Info 
Linker Name
Mc-Val-Cit-PABC
  Linker Info 
Conjugate Type
Reactive Cysteines
The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
Indication Phase 1 Phase 1/2 Phase 2 Phase 2/3 Phase 3 New Drug Application Approved
Bacteremia
1 Trials
Trial ID
NCT03162250; EudraCT2016-001880-35
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 20 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 1.62 ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4.
 [1]
Time to Maximum Concentration (Tmax) 2.56 h
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.76 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUClast.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.86 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUCinf.
 [1]
Maximum Observed Concentration (Cmax) 4.7 ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Time to Maximum Concentration (Tmax) 4.27 h
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 17.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 18.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Maximum Observed Concentration (Cmax) 16.6 ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Time to Maximum Concentration (Tmax) 4.81 h
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Maximum Observed Concentration (Cmax) 38.1 ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Time to Maximum Concentration (Tmax) 2.59 h
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Maximum Observed Concentration (Cmax) 45.5 ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Time to Maximum Concentration (Tmax) 4.32 h
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Distribution
Click To Hide/Show 15 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 5.76 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUClast.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.86 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUCinf.
 [1]
Volume of Distribution (Vd) 4.71 L
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 17.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 18.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Volume of Distribution (Vd) 3.82 L
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Volume of Distribution (Vd) 4.14 L
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Volume of Distribution (Vd) 4.82 L
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Volume of Distribution (Vd) 5.31 L
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Metabolism
Click To Hide/Show 10 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 5.76 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUClast.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.86 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 17.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 18.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Excretion
Click To Hide/Show 15 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 5.76 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUClast.
 [1]
Area Under the Concentration-Time Curve (AUC) 5.86 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4, AUCinf.
 [1]
Elimination Half-Life (t1/2) 5.3 day
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 5 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 17.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 18.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Elimination Half-Life (t1/2) 4.8 day
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 15 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.2 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 61.9 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Elimination Half-Life (t1/2) 4.28 day
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 50 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 123 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Elimination Half-Life (t1/2) 5.58 day
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 100 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Area Under the Concentration-Time Curve (AUC) 158 day*ug/mL
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [1]
Elimination Half-Life (t1/2) 6.14 day
Summary statistics of PK parameters for DSTA4637S conjugate in plasma, 150 mg/kg, n=4.
 [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  NCT02596399
PHASE1
A PHASE I, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED, SINGLE-ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY,TOLERABILITY, AND PHARMACOKINETICS OF DSTA4637S IN HEALTHY VOLUNTEERS
Undisclosed  NCT03162250
PHASE1
A Phase IB, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care Antibiotics

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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 [2]
Patients Enrolled
Eligible participants are healthy adults (BMI 18-32 kg/m2) with normal clinical/lab parameters, while exclusions encompass recent antibiotic use, vaccination, substance abuse, blood donation, pregnancy, HIV/HBV/HCV positivity, malignancy history (except non-melanoma skin cancer), and rifamycin hypersensitivity. Strict contraceptive measures are required.

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Administration Dosage
Participants will receive DSTA4637S intravenously on Day 1.
Related Clinical Trial
NCT Number NCT02596399  Clinical Status PHASE1
Clinical Description A PHASE I, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED, SINGLE-ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY,TOLERABILITY, AND PHARMACOKINETICS OF DSTA4637S IN HEALTHY VOLUNTEERS
Primary Endpoint
The study evaluates safety by monitoring adverse events (AEs) in participants receiving DSTA4637S, with data collected up to Day 85 post-treatment.
Other Endpoint
Pharmacokinetic analysis includes plasma/serum concentration measurements of DSTA4637S and anti-drug antibodies (ATAs), assessed longitudinally up to Day 85 to characterize drug exposure and immunogenicity.
Experiment 2 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Eligible participants must have a BMI of 18-40 kg/m2 and confirmed S. aureus bacteremia (positive culture within 120 hours) requiring ≥4 weeks of standard IV antibiotics. Key exclusions include unresected intravascular catheters, rifampicin-resistant S. aureus, prosthetic joint/vertebral infections, Child-Pugh B/C cirrhosis, polymicrobial bacteremia, immunosuppression, liver disease, abnormal ECG, recent biologic/experimental therapy, or anticipated cardiac surgery within 3 days post-randomization. Rifamycin-class antibiotics (except rifaximin) are prohibited during the study.

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Administration Dosage
DSTA4637S will be administered as an IV infusion at 3 dose levels.
Related Clinical Trial
NCT Number NCT03162250  Clinical Status PHASE1
Clinical Description A Phase IB, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care Antibiotics
Primary Endpoint
The study assesses safety by tracking the percentage of participants experiencing adverse events (AEs) over a monitoring period extending up to approximately 156 days from baseline.
Other Endpoint
Pharmacokinetic evaluations include measurements of Antibody-Conjugated dmDNA31 and DSTA4637S Total Antibody in plasma and serum, respectively, along with unconjugated dmDNA31 levels, all monitored from baseline up to approximately 156 days. Immunogenicity is evaluated via the percentage of participants developing anti-therapeutic antibodies (ATAs) to DSTA4637S during the same timeframe.

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References
Ref 1 A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti-Staphylococcus aureus Thiomab Antibody-Antibiotic Conjugate, in Healthy Volunteers
Ref 2 A Study to Investigate Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Healthy Volunteers
Ref 3 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Participants With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care (SOC) Antibiotics