General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0NTFBR
ADC Name
MEDI-3726
Synonyms
ADCT 401; ADCT-401; MEDI 3726; MEDI3726
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Organization
MedImmune LLC; AstraZeneca PLC
Drug Status
Phase 1
Indication
In total 1 Indication(s)
Prostate cancer [ICD11:2C82]
Phase 1
Drug-to-Antibody Ratio
2
Structure
Antibody Name
J591
 Antibody Info 
Antigen Name
Glutamate carboxypeptidase 2 (FOLH1)
 Antigen Info 
Payload Name
SG3199
 Payload Info 
Therapeutic Target
Human Deoxyribonucleic acid (hDNA)
 Target Info 
Linker Name
Mal-PEG8-Val-Ala-PABC
 Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Tesirine
Puchem SID
472420336
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
Composite Response Rate (RR)  NCT02991911
Phase 1
A phase 1/1b multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in subjects with metastatic castration resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.

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Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 15.86
%
PC-3 cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 36.17
%
LNCaP cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 45.68
%
PC-3 cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 68.2
%
LNCaP cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 76.95
%
LNCaP cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 93.55
%
22RV1 cells
Prostate carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 98.71
%
22RV1 cells
Prostate carcinoma
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]
Efficacy Data Composite Response Rate (RR)
12.10%
Patients Enrolled
Patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.
Administration Dosage
Administered at 0.015-0.30 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity; The MTD was not identified; the MAD was 0.30 mg/kg.
Related Clinical Trial
NCT Number NCT02991911  Clinical Status Phase 1
Clinical Description A phase 1/1b multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in subjects with metastatic castration resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 15.86% (Day 26) High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 36.17% (Day 19) Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.11 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 45.68% (Day 26) High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 4 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 68.20% (Day 19) Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.95% (Day 19) High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
Experiment 6 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.55% (Day 20) Negative PSMA expression (PSMA-)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma 22RV1 cells CVCL_1045
Experiment 7 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.71% (Day 20) Negative PSMA expression (PSMA-)
Method Description
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model PC-3 CDX model
In Vitro Model Prostate carcinoma 22RV1 cells CVCL_1045
References
Ref 1 Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody-Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide. Clin Cancer Res. 2021 Jul 1;27(13):3602-3609.
Ref 2 CMB-401

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