Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0QRDUT
ADC Name
AGS-16C3F
Synonyms
AGS-16C3F
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Organization
Agensys (Top20 MNC) (Originator)
Drug Status
Phase 2 (discontinued)
Drug-to-Antibody Ratio
4
Structure
Antibody Name
Anti-ENPP3 AGS-16C3F mAb
  Antibody Info 
Antigen Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3)
  Antigen Info 
Payload Name
MMAF
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Maleimido-caproyl
  Linker Info 
Conjugate Type
Random Cysteines
Combination Type
mafodotin
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
Kidney cancer
1 Trials
Trial ID
NCT01672775
1 Trials
Trial ID
NCT02639182
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 6 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 52.2 ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1.
 [1]
Maximum Observed Concentration (Cmax) 48.7 ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4.
 [1]
Time to Maximum Concentration (Tmax) 0.04 day
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1.
 [1]
Time to Maximum Concentration (Tmax) 0.05 day
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4.
 [1]
Area Under the Concentration-Time Curve (AUC) 200 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1, AUC0-21.
 [1]
Area Under the Concentration-Time Curve (AUC) 294 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4, AUC0-21.
 [1]
Distribution
Click To Hide/Show 2 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 200 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1, AUC0-21.
 [1]
Area Under the Concentration-Time Curve (AUC) 294 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4, AUC0-21.
 [1]
Metabolism
Click To Hide/Show 2 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 200 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1, AUC0-21.
 [1]
Area Under the Concentration-Time Curve (AUC) 294 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4, AUC0-21.
 [1]
Excretion
Click To Hide/Show 4 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 200 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1, AUC0-21.
 [1]
Area Under the Concentration-Time Curve (AUC) 294 day*ug/mL
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4, AUC0-21.
 [1]
Elimination Half-Life (t1/2) 7.28 day
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 1, AUC0-21.
 [1]
Elimination Half-Life (t1/2) 7.81 day
Summary of pharmacokinetic parameters of AGS-16C3F, Cycle 4, AUC0-21.
 [1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 7 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
stable disease (SD)  NCT01672775
PHASE1
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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Progression Free Survival  NCT02639182
PHASE2
A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
Partial Response (PR)  NCT01672775
PHASE1
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
PHASE2
A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
Disease control rate (DCR)  NCT02639182
PHASE2
A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
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 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data stable disease (SD)
50%
Patients Enrolled
Exclusion criteria comprise uncontrolled CNS metastases, investigational drug use within 4 weeks prior, AGS-16C3F hypersensitivity, thromboembolic events (≤3 months), severe cardiac conditions (e.g., CHF Class III/IV), major surgery within 4 weeks, pregnancy/lactation, HIV/hepatitis B/C positivity, active infections requiring systemic treatment, or recent eye surgery/cataracts affecting vision.

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Administration Dosage
ADCs were given q3w until PD or unacceptable toxicity.AGS-16M8F and AGS-16C3F studies treated 26 and 34 subjects in dose range 0.6 - 4.8 and 1.8 - 4.8 mg/kg, respectively.
Related Clinical Trial
NCT Number NCT01672775  Clinical Status PHASE1
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
The study evaluates the incidence of adverse events over 24 months and assesses pharmacokinetics (TAb, ADC, MMAF) including Ceoi/Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, Vss at specified time points up to Day 92. Secondary endpoints include antidrug antibody formation, tumor response (ORR, DCR), and bone scan changes during the study period.
Other Endpoint
Eligible participants include metastatic RCC patients (clear cell/non-clear cell or papillary histology) with prior anti-VEGFR therapy (clear cell) or ENPP3+ status (non-clear cell/papillary). Key requirements: measurable disease (RECIST 1.1), ECOG 0-1, adequate hematologic (ANC ≥1.5x109/L, platelet ≥100x109/L, Hb ≥9 g/dL), renal (creatinine ≤1.5xULN or GFR >50 mL/min), and hepatic function (AST/ALT ≤2.5xULN or ≤5xULN with metastases; bilirubin ≤1.5xULN). Contraception is mandated for participants of childbearing potential.

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Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Progression Free Survival
3.5 months
Patients Enrolled
Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

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Administration Dosage
Participants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.
Related Clinical Trial
NCT Number NCT02639182  Clinical Status PHASE2
Clinical Description A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
Primary Endpoint
The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC0- 21, t1/ 2) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

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Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Partial Response (PR)
8.80%
Patients Enrolled
Exclusion criteria comprise uncontrolled CNS metastases, investigational drug use within 4 weeks prior, AGS-16C3F hypersensitivity, thromboembolic events (≤3 months), severe cardiac conditions (e.g., CHF Class III/IV), major surgery within 4 weeks, pregnancy/lactation, HIV/hepatitis B/C positivity, active infections requiring systemic treatment, or recent eye surgery/cataracts affecting vision.

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Administration Dosage
ADCs were given q3w until PD or unacceptable toxicity.AGS-16M8F and AGS-16C3F studies treated 26 and 34 subjects in dose range 0.6 - 4.8 and 1.8 - 4.8 mg/kg, respectively.
Related Clinical Trial
NCT Number NCT01672775  Clinical Status PHASE1
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
The study evaluates the incidence of adverse events over 24 months and assesses pharmacokinetics (TAb, ADC, MMAF) including Ceoi/Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, Vss at specified time points up to Day 92. Secondary endpoints include antidrug antibody formation, tumor response (ORR, DCR), and bone scan changes during the study period.
Other Endpoint
Eligible participants include metastatic RCC patients (clear cell/non-clear cell or papillary histology) with prior anti-VEGFR therapy (clear cell) or ENPP3+ status (non-clear cell/papillary). Key requirements: measurable disease (RECIST 1.1), ECOG 0-1, adequate hematologic (ANC ≥1.5x109/L, platelet ≥100x109/L, Hb ≥9 g/dL), renal (creatinine ≤1.5xULN or GFR >50 mL/min), and hepatic function (AST/ALT ≤2.5xULN or ≤5xULN with metastases; bilirubin ≤1.5xULN). Contraception is mandated for participants of childbearing potential.

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Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
7.50%
Patients Enrolled
Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

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Administration Dosage
Participants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.
Related Clinical Trial
NCT Number NCT02639182  Clinical Status PHASE2
Clinical Description A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
Primary Endpoint
The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC0- 21, t1/ 2) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

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Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Disease control rate (DCR)
13.40%
Patients Enrolled
Exclusion criteria comprised prior axitinib/AGS-16C3F treatment, untreated or unstable brain metastases (>3 months post-radiation/surgery if treated), uncontrolled hypertension (>150/90), GI disorders affecting absorption, active ocular conditions (e.g., infections, corneal ulcers, glaucoma), strong CYP3A4/5 inhibitors/inducers use within 14 days, thromboembolic events (≤4 weeks unless anticoagulated), bleeding disorders (≤2 months), severe cardiac disease (NYHA Class III/IV, MI ≤6 months), major surgery ≤4 weeks, pregnancy/lactation, unresolved infections, or inability to comply with study protocols.

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Administration Dosage
Participants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.
Related Clinical Trial
NCT Number NCT02639182  Clinical Status PHASE2
Clinical Description A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
Primary Endpoint
The study assessed Progression-Free Survival (PFS) per RECIST v1.1 by investigator (up to 53 months) and central radiology review (up to 40 months), along with Objective Response Rate (ORR), Duration of Response (DOR), Overall Survival (OS), and Disease Control Rate (DCR). Pharmacokinetic parameters (Cmax, Ctrough, Tmax, AUC0- 21, t1/ 2) for ADC, TAb, and Cys-mcMMAF were evaluated over 21-day cycles. Adverse events (AEs) were monitored for 53 months, with serious AEs requiring intervention or hospitalization.

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Experiment 6 Reporting the Activity Date of This ADC [3]
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 7 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR) 7.50, 18.20 % 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 [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.1 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 [5]
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 [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 109.9 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 [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
146.5 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 A Randomized Phase II Study of AGS-16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma
Ref 2 A 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
Ref 3 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 4 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 5 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.