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| Primary information |
|---|
| ID | 10843 |
| Therapeutic ID | Th1206 |
| Protein Name | Nivolumab |
| Sequence | >Th1206_Nivolumab
QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYYADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
|
| Molecular Weight | 143597.4 |
| Chemical Formula | C6362H9862N1712O1995S42 |
| Isoelectric Point | 6.1-8.5 |
| Hydrophobicity | NA |
| Melting point | 80-90 ºC |
| Half-life | 26.7 days |
| Description | Nivolumab is a fully human IgG4 monoclonal antibody that acts as an immunomodulator by blocking ligand activation of programmed cell death 1 (PD-1) receptor on T cells. It is indicated for use in patients with unresectable (cannot be surgically removed) or metastatic melanoma who no longer respond to other drugs. Nivolumab is administered as an intravenous infusion over 60 minutes every 2 weeks. |
| Indication/Disease | Nivolumab is indicated for the treatment of unresectable or metastatic melanoma for patients who no longer respond to treatment with other drugs. It is intended for use in patients who have been previously treated with ipilimumab and is used for melanoma patients after treatment with ipilimumab and a BRAF inhibitor in patients whose tumors express BRAF V600 gene mutations. Historically there have been very few effective treatments for advanced melanoma, which is why this product was approved under an FDA accelerated program to allow earlier patient access. |
| Pharmacodynamics | Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity. |
| Mechanism of Action | Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death 1 (PD-1) receptor and selectively blocks interaction with its programmed death ligands PD-L1 and PD-L2. Upregulation of PD-1 ligands occurs in some tumors and signalling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumour tissue. The inhibitory effect of PD-1 and its ligands occurs through the promotion of apoptosis in antigen specific T cells while simultaneously blocking apoptosis in suppressor T cells. Blocking PD-1 activity has been shown to lead to decreased tumour growth in mouse tumour models. |
| Toxicity | Data regarding overdoses of nivolumab are not readily available.[L12129] Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema.[L12129] |
| Metabolism | There have not been formal studies regarding the specific metabolism of nivolumab but as a human monoclonal antibody, it has been suggested to be degraded to small peptides and individual amino acids.[L12618] |
| Absorption | Pharmacokinetic studies have suggested that nivolumab presents linear pharmacokinetics with a dose-proportional increase in peak concentration and AUC. The time to peak plasma concentration ranges between 1-4 hours.[A35187] The absorption pharmacokinetic properties respective to the administration of a dose of 10 mg/kg are reported to be Cmax, Tmax and AUC of 242 µg/kg, 2.99 hours and 68100 µg |
| The volume of distribution at steady state when a dose of 10 mg/kg of nivolumab is administered is reported to be 91.1 mL/kg.[A35285] At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L.[A35290] |
| Clearance | The estimated clearance rate of nivolumab is 9.4 mL/h.[A35284] The clearance rate seems to be increased according to body weight.[A35290] |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | US2013173223 |
| Date of Issue | 13-05-2013 |
| Date of Expiry | 13-05-2033 |
| Drug Interaction | Belimumab |
| Target | Programmed cell death protein 1 |
| Brand Name | Opdivo |
| Company | E.R. Squibb & Sons, L.L.C. |
| Brand Description | E.R. Squibb & Sons, L.L.C. |
| Prescribed For | OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma; Also for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma; approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials; and in combination with ipilimumab, is indicated for the treatment of patients with unresectable or metastatic melanoma. |
| Chemical Name | NA |
| Formulation | solution |
| Physical Appearance | Liquid |
| Route of Administration | Intravenous |
| Recommended Dosage | The recommended dose of OPDIVO as a single agent is 3 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. |
| Contraindication | NA |
| Side Effects | Immune-Mediated Pneumonitis; Immune-Mediated Colitis; Immune-Mediated Hepatitis; Immune-Mediated Endocrinopathies; Immune-Mediated Nephritis and Renal Dysfunction; Immune-Mediated Rash; Immune-Mediated Encephalitis; Other Immune-Mediated Adverse Reactions; Infusion Reactions; Complications of Allogeneic HSCT after OPDIVO. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |