Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0BBQSE
ADC Name
Enfortumab vedotin
Brand Name
Padcev
Synonyms
AGS-22C3;AGS-22CE;AGS-22M6E;AGS-22ME;AGS-M6;ASG-22CE;ASG-22M6E;ASG-22ME;ASP7465;DLE8519RWM;Enfortumab Vedotin-ejfv
   Click to Show/Hide
Organization
Astellas Pharma, Inc.; Seagen Inc.; Baxter Oncology GmbH
Drug Status
Approved (FDA): Dec 18, 2019
Indication
In total 7 Indication(s)
Urothelial cancer [ICD11:2C9Z]
Approved
Genitourinary tumor [ICD11:2C8Z]
NDA
Bladder cancer [ICD11:2C94]
Phase 3
Muscle-infiltrating bladder cancer [ICD11:2C94]
Phase 3
Epithelial tumor [ICD11:XH63D2]
Phase 2
Kidney cancer [ICD11:2C90-2C91]
Phase 2
Uterine cancer [ICD11:2C78]
Phase 2
Drug-to-Antibody Ratio
3.8
Structure
Antibody Name
Enfortumab
  Antibody Info 
Antigen Name
Nectin-4 (NECTIN4)
  Antigen Info 
Payload Name
Monomethyl auristatin E
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Mc-Val-Cit-PABC
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Vedotin
Absorption
For enfortumab vedotin (1.25 mg/kg), mean Cmax was 28 (ug/mL) and mean AUC was 111 (ug x day/mL) following the first treatment cycle (28 days). For unconjugated MMAE, mean Cmax was 4.8 (ug/mL) and mean AUC was 69 (ug x day/mL) following the first treatment cycle (28 days). The Tmax of MMAE is 1-3 days following the end of the infusion.
Distribution
The estimated steady-state volume of distribution is 11 L. MMAE was found to be 68-82% protein-bound in vitro. The specific proteins to which MMAE is bound have not been elucidated.
Metabolism
Given its structure, it is expected to be catabolized to smaller peptides, amino acids, unconjugated MMAE, and MMAE metabolites. MMAE is released from enfortumab vedotin via proteolytic cleavage by intracellular proteases and is metabolized primarily by CYP3A4 in vitro. The elimination half-lives of enfortumab vedotin and MMAE are 3.4 days and 2.4 days, respectively.
Elimination
In kinetic analyses of this drug, it was found that over a 1-week span, 17% of the total administered MMAE was retrieved in feces and 6% in urine. This excretion primarily involved the unchanged drug. The mean clearance of enfortumab vedotin and free MMAE was 0.10 L/h and 2.7 L/h, respectively. The clearance of MMAE appears to be limited by its rate of release from enfortumab vedotin.
Toxicity
Patients experiencing an overdose are likely at an increased risk of severe adverse effects such as significant nausea, vomiting, neuropathy, or rash. Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV.
Special Approval(s)
Accelerated approval(FDA); Breakthrough therapy(FDA)
Puchem SID
472406200 , 242651789 , 384585501 , 405067331 , 223370423 , 347911415 , 481101615
Drugbank ID
DB13007
ChEBI ID
CHEMBL3301589
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 6 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Objective Response Rate (ORR)  NCT04223856
Phase 3
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.

   Click to Show/Hide
Objective Response Rate (ORR)  NCT03219333
Phase 2
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.

   Click to Show/Hide
Objective Response Rate (ORR)  NCT03219333
Phase 2
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.

   Click to Show/Hide
Objective Response Rate (ORR)  NCT03070990
Phase 1
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.
Objective Response Rate (ORR)  NCT02091999
Phase 1
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.

   Click to Show/Hide
Undisclosed  NCT03474107
Phase 3
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).
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 30.8
%
Bladder cancer PDX model (PDX: AG-B1)
Tumor Growth Inhibition value (TGI) 
≈ 33.9
%
Pancreatic cancer PDX model (PDX: AG-Panc4)
Tumor Growth Inhibition value (TGI) 
≈ 45
%
Breast cancer PDX model (PDX: AG-Br7)
Tumor Growth Inhibition value (TGI) 
≈ 68.8
%
Pancreatic cancer PDX model (PDX: AG-Panc4)
Tumor Growth Inhibition value (TGI) 
≈ 80.7
%
Bladder cancer PDX model (PDX: AG-B1)
Tumor Growth Inhibition value (TGI) 
≈ 93.8
%
Breast cancer PDX model (PDX: AG-Br7)
Tumor Growth Inhibition value (TGI) 
≈ 97.6
%
Breast cancer orthotopic PDX model (PDX: AG-Br7)
Tumor Growth Inhibition value (TGI) 
≈ 97.7
%
Breast cancer orthotopic PDX model (PDX: AG-Br7)
Tumor Growth Inhibition value (TGI) 
≈ 98.7
%
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
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 26
%
NCI-H322M cells
Minimally invasive lung adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 83.6
%
NCI-H322M cells
Minimally invasive lung adenocarcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
1.2
ng/mL
PC-3 cells
Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50) 
3.4
ng/mL
PC-3 cells
Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50) 
4.7
ng/mL
PC-3 cells
Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50) 
37.8
ng/mL
T-47D cells
Invasive breast carcinoma
Full List of Activity Data of This Antibody-drug Conjugate
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 [1]
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).

   Click to Show/Hide
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 [2]
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 [3]
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 [4]
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 [5]
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 [6]
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).

   Click to Show/Hide
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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 [7]
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
References
Ref 1 Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023 Jan 1;41(1):22-31.
Ref 2 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 3 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 4 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 5 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 6 Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021 Mar 25;384(12):1125-1135.
Ref 7 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.

If you find any error in data or bug in web service, please kindly report it to Dr. Shen et al.