General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0UDFEK
ADC Name
dS-1062
Synonyms
datopotamab deruxtecan (DS-1062)
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Organization
ASTRAZENECA UK LIMITED | DAIICHI SANKYO COMPANY
Drug Status
Investigative
Drug-to-Antibody Ratio
3.5-4.5
Structure
Antibody Name
anti-TROP2 antibody
 Antibody Info 
Antigen Name
Tumor-associated calcium signal transducer 2 (TACSTD2)
 Antigen Info 
Payload Name
DX-8951 derivative (DXd)
 Payload Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
 Target Info 
Linker Name
Mc-Gly-Gly-Phe-Gly
 Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Deruxtecan
General Information of The Activity Data Related to This ADC
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth lnhibition value (TGl) 
72
%
CTG-3718 human patient-derived xenograft (PDX) model
Tumor Growth lnhibition value (TGl) 
88
%
CTG-3303 human patient-derived xenograft (PDX) model
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth lnhibition value (TGl) 
82
%
Undisclosed Undisclosed
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) 72% Positive TROP2 expression (TROP2+++/++)
Method Description
This PDX was obtained in accordance with appropriate consent procedures. This ovarian PDX model was subcutaneously passaged in vivo as fragments from animal to animal in nude mice. When tumors reached approximately 250 mm 3 similar-sized tumors were randomly assigned to treatment groups, DS-1062 was administered as a single dose at 10 mg/kg on day 1. Duration of dosing was 21 days. TGI responses (Day 28 TGI%) was measurede.

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In Vivo Model CTG-3718 human patient-derived xenograft (PDX) model
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) 88% Positive TROP2 expression (TROP2+++/++)
Method Description
Female Nude mice (Charles River) aged 5-8 weeks were used, following 7 days acclimatisation before entry into the study. The human patient-derived xenograft (PDX) model, CTG-3303, was established from fragments of freshly resected tumor of a triple negative breast cancer (TNBC) patient whom relapsed on treatment with PARP inhibitor talazoparib. This PDX was obtained in accordance with appropriate consent procedures. This TNBC PDX model was subcutaneously passaged in vivo as fragments from animal to animal in nude mice. When tumors reached approximately 250 mm 3 , similar-sized tumors were randomly assigned to treatment groups. DS-1062 was administered as a single dose at 10 mg/kg on day 1. Duration of dosing schedule was 21 days. TGI responses (Day 46 TGI%) was measurede.

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In Vivo Model CTG-3303 human patient-derived xenograft (PDX) model
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) 82% Positive TROP2 expression (TROP2+++/++)
Method Description
Nude mice (Charles River) aged 5-8 weeks wereused,following 7 days acclimatisation before entry intothe study.5x106 NCI-N87 tumor cells (gastric cancercell line) (1:1 in Matrigel)were implantedsubcutaneously onto the flank of the female Nude mice.When tumors reached approximately 250 mm,similar-sizedtumors were randomly assigned to treatment groups, DS-1062 was administered as a single dose at 10 mg/kg on day 1. Duration of dosing schedule was 21 days.

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In Vivo Model NCI-N87 Xenograft model
References
Ref 1 Combination of antibody-drug conjugate and PARP1 selective inhibitor