Source of information: Drugbank (External Link). Last updated on: 3rd July 18
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Active Ingredient / Synonyms
Durvalumab | Durvalumab |
Durvalumab is a a human monoclonal antibody that blocks programmed death ligand 1 (PD-L1), or CD 274. In May, 2017 it received FDA approval for previously treated patients with locally advanced or metastatic cancer in the urinary system (as Imfinzi). It is shown to be effective in patients with continued disease progression after the platinum-based chemotherapy. This drug has a relatively tolerable safety profile and its structural modification advantageously prevents the induction of antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) [L749].
Durvalumab is indicated for patients with urothelial carcinoma, such as urinary bladder, urethra or ureter cancer. Patients with prolonged disease progression due to failed platinum-based chemotherapy such as cisplatin and carboplatin are most likely to benefit from durvalumab treatment. Its clinical effectiveness is especially enhanced in PD-L1-positive patient groups [A19123].
Mechanism of Action
Durvalumab is a human immunoglobulin G1 kappa (IgGIk) monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. PD1 signalling pathway serves to physiologically limit the activity of T cells and autoimmune or inflammatory responses in the body however can be a mechanism of immunity resistance by tumor cells. Blockage of ligand-mediated PD1 pathway enhances further T cell activation, effector T cell proliferation, NK cell activity and cytokine production to minimize the growth of locally advancing or metastasizing solid tumors.
PD-L1 (programmed cell death ligand 1) is a ligand of PD-1 receptor on activated T cells. Tumor cells and tumor-associated immune cells express this inhibitory immune checkpoint molecule that interrupts normal signalling of T cell and subsequent immune responses in the tumor microenvironment by binding to PD-1 receptors. As a novel anticancer immunotherapy, durvalumab enhances T cell responses at tumor sites. Durvalumab acts as a selective antibody against this ligand and prevents its interaction to the PD-1 receptor and promotes normal antitumor T-cell mediated immune activity. It is also referred to as an immune checkpoint inhibitor.
Mean Vd approximately 5.6 L with 17% coefficient of variation.
Most likely to be degraded into peptides and amino acids by circulating phagocytic cellsor by target antigen-containing cells [A19126].
Mean elimination half-life is approximately 12 days with 23.2% coefficient of variation.
Mean steady state clearance is approximately 8.24 mL/h (37.3% coefficient of variation).
Many toxic effects of durvalumab therapy are immune-mediated inflammation in various tissues including pneumonitis, hepatitis and colitis. Disturbances in endocrine system are possible adverse effects such as hypo/hyperthyroidism, type I diabetes mellitus and adrenal insufficiency. Cessation of therapy is recommended in case of any immune-mediated or infusion-related adverse reactions. Animal studies suggest a possibility of embryo-fetal toxicity.
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