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| Primary information |
|---|
| ID | 13839 |
| Therapeutic ID | Th1440 |
| Protein Name | Avelumab |
| Sequence | >Th1440_Avelumab
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFYADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 142 |
| Chemical Formula | C6374H9898N1694O2010S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal half-life is approximately 6.1 days in patients receiving 10 mg/kg. |
| Description | Avelumab is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). It is a fully human anti-PD immunoglobulin G1 (IgG1) lambda monoclonal antibody with antineoplastic actions. It was granted accelerated approval in March 2017 under the name Bavencio. |
| Indication/Disease | Indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). |
| Pharmacodynamics | Avelumab is a whole antibody that binds the immunosuppressive programmed death-ligand 1 and inhibits the interaction between PD-1 and PD-L1. It prevents the formation of a PD-1/PD-L1 receptor/ligand complex that normally leads to inhibition of CD8+ T cells, and therefore inhibition of an immune reaction. Alevumab is an immunotherapeutic and antineoplastic agent that belongs to the group of immune checkpoint blockade cancer therapies. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and may induce antibody-dependent cell-mediated cytotoxicity (ADCC). |
| Mechanism of Action | PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Avelumab binds PD-L1 through the FG loops [A19625] and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth. |
| Toxicity | Avelumab toxicity includes the possibility of experiencing potentially fatal infusion reactions and/or immunogenic reactions like pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis, among others. Other common adverse effects include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. |
| Metabolism | Avelumab undergoes nonspecific proteolytic degradation. |
| Absorption | The exposure of avelumab increased dose-proportionally in the dose range of 10 to 20 mg/kg every 2 weeks. Steady-state concentrations of avelumab were reached after approximately 4 to 6 weeks (2 to 3 cycles) of repeated dosing, and the systemic accumulation was approximately 1.25-fold. |
| The geometric mean volume of distribution at steady state for a subject receiving 10 mg/kg is 4.72 L. |
| Clearance | The total systemic clearance is approximately 0.59 L/day. |
| Categories | Antibodies, Monoclonal |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Programmed cell death 1 ligand 1 |
| Brand Name | Bavencio |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Intravenous |
| Chemical Name | 20 mg/1mL |
| Formulation | NA |
| Physical Appearance | fatigue/lack of energy, musculoskeletal pain (back pain, neck pain, pain in extremities), diarrhea, nausea, infusion-related reactions (chills, fever, back pain, hypersensitivity reactions and low blood pressure), rash and skin redness, decreased appetite, swelling of the extremities, joint pain, constipation, abdominal pain, vomiting, itching, weight loss, cough, shortness of breath, dizziness, headache, and high blood pressure (hypertension). |
| Route of Administration | Bavencio is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Bavencio is used to treat a type of skin cancer called Merkel cell carcinoma in adults and children at least 12 years old, when the cancer has spread to other parts of the body (metastatic). Bavencio... |
| Recommended Dosage | BAVENCIO (avelumab) is indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies]. |
| Contraindication | NA |
| Side Effects | Avelumab is a programmed death ligand1 (PD-L1) blocking antibody. Avelumab- is a human IgG1 lambda monoclonal antibody produced in Chinese hamster ovary cells and has a molecular weight of approximately 147 kDa. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |