Antibody Information

General Information of This Antibody
Antibody ID
ANI0LTVSQ
Antibody Name
Enfortumab
Organization
Astellas Pharma, Inc.
Indication
Neoplasms
Synonyms
AGS-22C3
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Nectin-4 (NECTIN4)
  Antigen Info 
ChEMBI ID
CHEMBL3301579
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVSYISSSSSTIYY
ADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAYYYGMDVWGQGTTVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
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Light Chain Sequence
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAASTLQSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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The Activity Data of This Antibody
Antibody Activity Information 1 [1]
Dissociation Constant (Kd)
1
pM
T-47D cells CVCL_0553 
Antigen Expression High Nectin-4 expression (NECTIN4+++)
Antibody Function Confirm the effect of the drug conjugation with the anti-Nectin-4 Ab on binding activity to target.
Antibody Antigen Binding Assay Flow cytometry.
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Enfortumab vedotin [Approved]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
73.30%
Patients Enrolled
Histologically documented locally advanced/metastatic urothelial carcinoma (la/mUC) (including squamous differentiation and mixed cell types), an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a 5-point scale; higher scores indicate greater disability), and an investigator-assessed life expectancy of 3 or more months.
Administration Dosage
1.25 mg/kg once daily on days 1 and 8 intravenously once daily in 3-week cycles.
Related Clinical Trial
NCT Number NCT04223856  Clinical Status Phase 3
Clinical Description
An open-label, randomized, controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab versus chemotherapy alone in previously untreated locally advanced or metastatic urothelial cancer.
Primary Endpoint
Safety: Seven patients (15.60%) experienced a serious TRAE, with no serious TRAE occurring more than once. TRAEs led to dose reductions in 14 (31.10%) patients and discontinuations in 11 (24.40%) patients and were not mutually exclusive. Peripheral sensory neuropathy was the most common TRAE leading to either dose reduction (six patients, 13.30%) or treatment discontinuation (four patients, 8.90%). No patients discontinued therapy because of a skin reaction or hyperglycemia. One patient (2.20%) died because of a TRAE (multiple organ dysfunction syndrome).

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Other Endpoint
The confirmed objective response rate after a median of nine cycles was 73.30% with a complete response rate of 15.60%. The median DOR and median OS were 25.60 months and 26.10 months, respectively.
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
44.00%
High Nectin-4 expression (NECTIN4+++)
Patients Enrolled
Locally advanced or metastatic urothelial carcinoma who were previously treated with platinum chemotherapy and antiPD-1/L1 therapy.
Administration Dosage
1.25 mg/kg (intravenously on days 1, 8, and 15 of every 28-day cycle).
Related Clinical Trial
NCT Number NCT03219333  Clinical Status Phase 2
Clinical Description
A single-arm, open-label, multicenter study of enfortumab vedotin (ASG-22CE) for Treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor (CPI) Therapy.
Primary Endpoint
Confirmed objective response rate was 44.00% (95% CI, 35.10% to 53.20%), including 12.00% complete responses.
Other Endpoint
Median duration of response was 7.60 months (range, 0.95 to 11.30 months).
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR)
51.68%
High Nectin-4 expression (NECTIN4+++)
Patients Enrolled
Locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors; an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting.
Administration Dosage
Intravenously at a dose of 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle.
Related Clinical Trial
NCT Number NCT03219333  Clinical Status Phase 2
Clinical Description
A single-arm, open-label, multicenter study of enfortumab vedotin (ASG-22CE) for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor (CPI) therapy.
Primary Endpoint
The confirmed objective response rate was 51.68% (46 of 89 patients; 95% CI 41.00-62.00), with 18 (20.22%) of 89 patients achieving a complete response and 28 (31.46%) achieving a partial response.
Other Endpoint
Duration of response, progression-free survival, objective response rate, overall survival, safety, and tolerability, plasma or serum pharmacokinetic parameters of enfortumab vedotin, MMAE, and total antibody, and incidence of antitherapeutic antibody to enfortumab vedotin.
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Objective Response Rate (ORR)
35.30%
Moderate Nectin-4 expression (NECTIN4++)
Patients Enrolled
Histologically confirmed, locally advanced or metastatic transitional cell carcinoma of the urothelium (ie, cancer of the bladder, renal pelvis, ureter, or urethra), or UC with squamous differentiation or mixed cell types and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Administration Dosage
1.00 mg/kg (Arm A) or 1.25 mg/kg (Arm B) on Days 1, 8, and 15 of each 28-day cycle.
Related Clinical Trial
NCT Number NCT03070990  Clinical Status Phase 1
Clinical Description
An open-label, randomized, phase 1 safety and pharmacokinetic study of enfortumab vedotin (ASG-22CE) in Japanese patients with locally advanced or metastatic urothelial carcinoma.
Primary Endpoint
Safety/tolerability of EV, EV PK profile.
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Objective Response Rate (ORR)
43.00%
High Nectin-4 expression (NECTIN4+++)
Patients Enrolled
Nectin-4positive solid tumors, including mUC, who progressed on 1 prior chemotherapy regimen or who were ineligible for cisplatin chemotherapy.
Administration Dosage
Weight-based doses (0.50, 0.75, 1.00, and 1.25 mg/kg) through 30-minute infusion on days 1, 8, and 15 of a 28-day cycle.
Related Clinical Trial
NCT Number NCT02091999  Clinical Status Phase 1
Clinical Description
A phase 1 study of the safety and pharmacokinetics of escalating doses of ASG-22CE given as monotherapy in subjects with metastatic urothelial cancer and other malignant solid tumors that express nectin-4.
Primary Endpoint
The determination of safety/tolerability, recommended phase II dose (RP2D), and pharmacokinetic (PK) profile of EV.
Other Endpoint
Antitumor activity,including confirmed investigator-assessed ORR (RECIST version 1.1), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Experiment 6 Reporting the Activity Date of This ADC [7]
Patients Enrolled
Histologically or cytologically confirmed urothelial carcinoma (including differentiation in squamous cells or in multiple cell types), radiologically documented metastatic or unresectable locally advanced disease at baseline, and an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 (scores range from 0 to 4, with higher scores indicating greater disability).

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Administration Dosage
Intravenous infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Related Clinical Trial
NCT Number NCT03474107  Clinical Status Phase 3
Clinical Description
An open-label, randomized phase 3 study to evaluate enfortumab vedotin vs chemotherapy in subjects with previously treated locally advanced or metastatic urothelial cancer (EV-301).
Primary Endpoint
Overall survival was prolonged with enfortumab vedotin compared with chemotherapy (HR=0.70 [95% CI: 0.56-0.89];.
Other Endpoint
Median overall survival: 12.88 vs 8.97 months, respectively). Progression-free survival was also longer in the enfortumab vedotin group compared with the chemotherapy group (HR=0.62 [95% CI: 0.51-0.75]; P<0.00001; median progression-free survival: 5.55 vs 3.71 months, respectively).
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 30.80% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a bladder cancer cell with Nectin-4 high expression, dosed every 4 days at 0.4 mg/kg for 5 times.
In Vivo Model Bladder cancer PDX model (PDX: AG-B1)
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 33.90% (Day 24) Moderate Nectin-4 expression (NECTIN4++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a pancreatic cancer cell with Nectin-4 moderate expression, dosed every 4 days at 1 mg/kg for 6 times.
In Vivo Model Pancreatic cancer PDX model (PDX: AG-Panc4)
Experiment 3 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 45.00% (Day 24) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a breast cancer cell with Nectin-4 high expression, dosed every 4 days at 1 mg/kg for 6 times.
In Vivo Model Breast cancer PDX model (PDX: AG-Br7)
Experiment 4 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 68.80% (Day 24) Moderate Nectin-4 expression (NECTIN4++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a pancreatic cancer cell with Nectin-4 moderate expression, dosed every 4 days at 3 mg/kg for 6 times.
In Vivo Model Pancreatic cancer PDX model (PDX: AG-Panc4)
Experiment 5 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.70% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a bladder cancer cell with Nectin-4 high expression, dosed every 4 days at 0.8 mg/kg for 5 times.
In Vivo Model Bladder cancer PDX model (PDX: AG-B1)
Experiment 6 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.80% (Day 24) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a breast cancer cell with Nectin-4 high expression, dosed every 4 days at 3 mg/kg for 6 times.
In Vivo Model Breast cancer PDX model (PDX: AG-Br7)
Experiment 7 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.60% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in orthotopic PDX models of a breast cancer cell with Nectin-4 high expression, established in mammary fat pads of SCID mice, dosed single 10 mg/kg.
In Vivo Model Breast cancer orthotopic PDX model (PDX: AG-Br7)
Experiment 8 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.70% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in orthotopic PDX models of a breast cancer cell with Nectin-4 high expression, established in mammary fat pads of SCID mice, dosed twice 5 mg/kg.
In Vivo Model Breast cancer orthotopic PDX model (PDX: AG-Br7)
Experiment 9 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.70% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a bladder cancer cell with Nectin-4 high expression, single 4 mg/kg dose.
In Vivo Model Bladder cancer PDX model (PDX: AG-B1)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 26.00% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a lung adenocarcinoma cell with Nectin-4 high expression, dosed every 4 days at 1 mg/kg for 5 times.
In Vivo Model NCI-H322M CDX model
In Vitro Model Minimally invasive lung adenocarcinoma NCI-H322M cells CVCL_1557
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.60% (Day 18) High Nectin-4 expression (NECTIN4+++)
Method Description
AGS-22M6E induces efficient tumor cell killing in PDX models of a lung adenocarcinoma cell with Nectin-4 high expression, dosed every 4 days at 3 mg/kg for 5 times.
In Vivo Model NCI-H322M CDX model
In Vitro Model Minimally invasive lung adenocarcinoma NCI-H322M cells CVCL_1557
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.20 ng/mL
Method Description
The inhibitory activity of AGS-22M6, AGS-22M6E ADC, and an isotype control ADC were added to various cancer cell lines in vitro and cell viability was measured after 5 days.
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.40 ng/mL
Method Description
The inhibitory activity of AGS-22M6, AGS-22M6E ADC, and an isotype control ADC were added to various cancer cell lines in vitro and cell viability was measured after 5 days.
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 3 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.70 ng/mL
Method Description
The inhibitory activity of AGS-22M6, AGS-22M6E ADC, and an isotype control ADC were added to various cancer cell lines in vitro and cell viability was measured after 5 days.
In Vitro Model Prostate carcinoma PC-3 cells CVCL_0035
Experiment 4 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
37.80 ng/mL
Method Description
The inhibitory activity of AGS-22M6, AGS-22M6E ADC, and an isotype control ADC were added to various cancer cell lines in vitro and cell viability was measured after 5 days.
In Vitro Model Invasive breast carcinoma T-47D cells CVCL_0553
WO2022057651A1 ADC-22 [Investigative]
 ADC Info 
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 [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 21) Positive NECTIN4 expression (NECTIN4 +++/++)
Method Description
Conjugates of the exemplary antibodies were tested using an established xenograft model implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 10 mg/kg of one of the conjugates listed above or with PBS only.
In Vivo Model NCI-H322M CDX model
In Vitro Model Minimally invasive lung adenocarcinoma NCI-H322M cells CVCL_1557
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Effective Concentration (EC50)
229.20 ng/mL
Positive NECTIN4 expression (NECTIN4 +++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Invasive breast carcinoma T-47D cells CVCL_0553
Experiment 2 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Effective Concentration (EC50)
2.05 ug/mL
High NECTIN4 expression (NECTIN4 +++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
References
Ref 1 Phase I Study of DSTP3086S, an Antibody-Drug Conjugate Targeting Six-Transmembrane Epithelial Antigen of Prostate 1, in Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019 Dec 20;37(36):3518-3527.
Ref 2 Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023 Jan 1;41(1):22-31.
Ref 3 Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019 Oct 10;37(29):2592-2600.
Ref 4 Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872-882.
Ref 5 A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Invest New Drugs. 2020 Aug;38(4):1056-1066.
Ref 6 EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol. 2020 Apr 1;38(10):1041-1049.
Ref 7 Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021 Mar 25;384(12):1125-1135.
Ref 8 Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016 May 15;76(10):3003-13.
Ref 9 Anti-nectin-4 antibody, conjugate including same, and application thereof; 2022-03-24.

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