Enfortumab Overview
Introduction Mechanisms Clinical Projects Approved Drugs
Introduction of Enfortumab
Enfortumab is a fully human IgG1 kappa antibody targeting Nectin-4 that is designed for targeted therapy against ureteral cancer cells. It received U.S. Food and Drug Administration accelerated approval in 2019 for the treatment of ureteral cancer (PADCEV). This approval extends to patients who cannot undergo cisplatin-containing chemotherapy.
Biological and Chemical Properties of Enfortumab
Protein Chemical Formula
C6642H10284N1742O2063S46
Protein Average Weight
Approximately 149,000 Da
Mechanism of Action of Enfortumab
Enfortumab is an innovative monoclonal antibody-drug conjugate (ADC) that targets and kills cancer cells expressed Nectin-4. It carries the cytotoxic agent monomethyl auristatin E (MMAE) and targets cells expressing Nectin-4, a cell-adhesion molecule frequently found in high levels on tumor cells, especially in ureteral cancer. Enfortumab specifically binds to Nectin-4, promoting the entry of the ADC-Nectin-4 complex into the cell. Once inside, MMAE is released through proteolytic cleavage, disrupting the intracellular microtubule network and ultimately inducing cell death.
Targeting Nectin-4
Nectin-4, also known as poliovirus receptor-related protein 4 (PVRL4), is a type I transmembrane protein and a member of the immunoglobulin-like adhesion molecules family that participates in cell adhesion. This adhesion plays a significant role in biochemical reactions, including immune modulation, host-pathogen interactions, and immune evasion. Nectin-4 is highly expressed on cancer cells, particularly in ureteral cancer, while its expression is moderate in normal skin cells. This overexpression contributes to tumor cell growth and proliferation.
Conjugation with MMAE
MMAE, a synthetic derivative of dolastatin-10, is structurally similar to taxanesinhibits tubulin polymerization, thereby disrupting microtubule dynamics. The Enfortumab-MMAE complex binds with high affinity to Nectin-4 on the cell surface, allowing for targeted delivery of the cytotoxic agent. Once inside the cell, MMAE is released from Enfortumab, leading to the disruption of the microtubule network, arresting cell cycle progression, and ultimately triggering programmed cell death.
Clinical Projects of Enfortumab*
| NCT ID | Study Title | Study Status | Conditions | Sponsor | Start Date |
| NCT06104618 | Enfortumab Vedotin for the Treatment of Patients With Metastatic or Unresectable Squamous Cell Carcinoma of the Penis | RECRUITING | Metastatic Penile Squamous Cell Carcinoma | Mayo Clinic | 2023/12/21 |
| NCT05014139 | A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer | RECRUITING | Urinary Bladder Neoplasms | Astellas Pharma Global Development, Inc. | 2021/12/07 |
| NCT05915351 | Enfortumab Vedotin in Previously Treated Locally Advanced or Metastatic Pancreatic Cancer | RECRUITING | Pancreatic Adenocarcinoma | University of Kansas Medical Center | 2023/06/30 |
| NCT04995419 | A Study to Evaluate Enfortumab Vedotin (ASG-22CE) in Chinese Participants With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and Programmed Cell Death Protein-1 (PD 1) / (Programmed Death Ligand-1 (PD-L1) Inhibitor Therapy | ACTIVE, NOT RECRUITING | Metastatic Urothelial Cancer | Astellas Pharma China, Inc. | 2021/07/22 |
| NCT04754191 | Enfortumab Vedotin as Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer | RECRUITING | Prostate Cancer | University of Utah | 2022/02/03 |
| NCT06011954 | A Study to Survey Adults in South Korea With Cancer Who Receive PADCEV Injection | RECRUITING | Urothelial Cancer | Astellas Pharma Korea, Inc. | 2023/11/01 |
* The table is excerpted from the following website:
https://clinicaltrials.gov/ct2/results?cond=&term=Enfortumab
Approved Drugs of Enfortumab**
| INN (trade name) | Therapeutic area | Dose | Strength | Route | Company | Marketing start | Market |
| PADCEV | Urothelial Cancer | Injection | 20 mg/vial | Intravenous | Astellas Pharma US, Inc. | 2019-12-18 |
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| PADCEV | Urothelial Cancer | Injection | 30 mg/vial | Intravenous | Astellas Pharma US, Inc. | 2019-12-18 |
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** The information in the table is collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process
For research use only. Not intended for any clinical use.
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