Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0QRDUT
ADC Name
AGS-16C3F
Synonyms
Anti-ENPP3-MMAF; AGS-16F; AGS-16M8F; AGS 16C3F; AGS 16C3F; AGS16C3F
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Organization
Agensys, Inc.; Astellas Pharma, Inc.
Drug Status
Terminated in phase 2
Indication
In total 1 Indication(s)
Renal cell carcinoma [ICD11:2C90]
Terminated in phase 2
Drug-to-Antibody Ratio
4.2
Structure
Antibody Name
Anti-ENPP3 AGS-16C3F mAb
  Antibody Info 
Antigen Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3)
  Antigen Info 
Payload Name
Monomethyl auristatin F
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Maleimido-caproyl
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
McMMAF
Puchem SID
472422115 , 440234978
Drugbank ID
DB17551
DrugMap ID
DM2POHA
TTD ID
D0XT5Q
ChEBI ID
CHEMBL4594455
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
Partial Response (PR)  NCT01672775
Phase 1
A phase 1, open label, multi-center study to assess the safety, pharmacokinetics and effectiveness of AGS-16C3F monotherapy in subjects with renal cell carcinoma (RCC) of clear cell or papillary histology.

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Objective Response Rate (ORR)  NCT02639182
Phase 2
A multi-center, open label, randomized phase 2 study of AGS-16C3F vs. axitinib in metastatic renal cell carcinoma.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
1.1
nM
ROSA KIT D816V cells
Normal
Half Maximal Inhibitory Concentration (IC50) 
2.73
nM
ROSA KIT D816V Gluc cells
Mast-cell sarcoma
Half Maximal Inhibitory Concentration (IC50) 
109.9
nM
HMC-1.1 cells
Mast cell leukemia
Half Maximal Inhibitory Concentration (IC50) 
146.5
nM
HMC-1.2 cells
Mast cell leukemia
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]
Efficacy Data Partial Response (PR) 23.08% High ENPP3 expression (ENPP3+++)
Patients Enrolled
Metastatic renal cell carcinoma (MRCC), Eastern Cooperative Oncology Group (ECOG) performance status 1, adequate organ and bone marrow function.
Administration Dosage
AGS-16M8F was administered intravenously every 3 weeks at 5 dose levels ranging from 0.60 to 4.80 mg/kg until unacceptable toxicity or progression. A second study with AGS-16C3F started with the AGS-16M8F bridging dose of 4.80 mg/kg given every 3 weeks.
Related Clinical Trial
NCT Number NCT01672775  Clinical Status Phase 1
Clinical Description A phase 1, open label, multi-center study to assess the safety, pharmacokinetics and effectiveness of AGS-16C3F monotherapy in subjects with renal cell carcinoma (RCC) of clear cell or papillary histology.
Primary Endpoint
In the AGS-16C3F study (n = 34),the MTD was 3.60 mg/kg,but this was not tolerated. The 1.80 mg/kg dose was determined to be safe and was associated antitumor response.
Other Endpoint
3 subjects at 1.80 mg/kg achieved durable PR (3/13, 23.08%). The disease control rate at 1.80 mg/kg was 92.30% (N=12/13). The disease control rate for the entire study was 58.82% (N=20/34).
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR) 7.50% (AGS16C3F), 18.20% (axitinib) Moderate ENPP3 expression (ENPP3++)
Patients Enrolled
Advanced renal cell carcinoma (RCC).
Administration Dosage
Intravenous AGS-16C3F 1.80 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose).
Related Clinical Trial
NCT Number NCT02639182  Clinical Status Phase 2
Clinical Description A multi-center, open label, randomized phase 2 study of AGS-16C3F vs. axitinib in metastatic renal cell carcinoma.
Primary Endpoint
Median PFS=2.90 months (95% CI,2.00-4.00) for AGS16C3F,Median PFS=5.7 months (95% CI,5.30-9.10) for axitinib.
Other Endpoint
Disease Control Rate (DCR)=13.40% (95% CI,6.3-24.0) for AGS16C3F, Disease Control Rate (DCR)=22.70% (95% CI,13.30-34.70) for axitinib. Median duration of Response (mDoR)=6.80 months (95% CI,3.80-18.40) for AGS16C3F, Median duration of Response (mDoR)=6.7 months (95% CI,1.80-9.20) for axitinib. Objective Response Rate (ORR)=7.50% (95% CI,2.50-16.60) for AGS16C3F, Objective Response Rate (ORR)=18.20% (95% CI,9.80-29.60) for axitinib. Median Overall Survival (mOS)=13.10 months for AGS16C3F, Median Overall Survival (mOS)=15.40 months for axitinib.

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Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.10 nM
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Normal ROSA KIT D816V cells CVCL_5G50
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 2.73 nM Moderate ENPP3 expression (ENPP3++)
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast-cell sarcoma ROSA KIT D816V Gluc cells Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 109.90 nM High ENPP3 expression (ENPP3+++)
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast cell leukemia HMC-1.1 cells CVCL_H206
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
146.50 nM
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast cell leukemia HMC-1.2 cells CVCL_H205
References
Ref 1 Phase I Trials of Anti-ENPP3 Antibody-Drug Conjugates in Advanced Refractory Renal Cell Carcinomas. Clin Cancer Res. 2018 Sep 15;24(18):4399-4406.
Ref 2 A Randomized Phase II Study of AGS-16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma. Oncologist. 2021 Mar;26(3):182-e361.
Ref 3 In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis. Blood Adv. 2019 Feb 26;3(4):633-643.

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