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1815 details
Primary information
ThPP IDTh1206
Therapeutic Peptide/Protein NameNivolumab
SequenceHeavy Chain Sequence QVQLVESGGGVVQPGRSLRLDCKASGITF view full sequnce in fasta
Functional ClassificationIIIc
Molecular Weight143597.3811
Chemical FormulaC6362H9862N1712O1995S42
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half Life26.7 days
DescriptionNivolumab 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/DiseaseNivolumab 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.
PharmacodynamicsCombined 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 ActionNivolumab 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.
ToxicityBased on data from animal studies, there is risk of fetal harm when administered to pregnant women. It is therefore advisable for pregnant women to use contraception during treatment and for 5 months afterwards. There have been reported cases of severe pneumonitis or interstitial lung disease, including fatal cases, with the use of nivolumab during clinical trials. Therefore, patients taking this drug should be monitored for signs and symptoms of pneumonitis. During clinical trials there have also been reports of the development of immune-mediated colitis, immune-mediated hepatitis with increased liver test abnormalities, immune-mediated nephritis and renal dysfunction, immune-mediated hypothyroidism and hyperthyroidism, and rare cases of other immune-mediated reactions such as pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal insufficiency, and facial and abducens nerve paresis.
MetabolismAs nivolumab is an antibody, the expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.
AbsorptionThe intended route of administration is intravenous, therefore bioavailability is expected to be 100%.
Volume of Distribution8.0 L
Clearance9.5 mL/hr
CategoriesAntineoplastic and Immunomodulating Agents
Patents NumberUS2013173223
Date of Issue41407
Date of Expiry48712
Drug InteractionBelimumab
TargetProgrammed cell death protein 1
Information of corresponding available drug in the market
Brand NameOpdivo
CompanyE.R. Squibb & Sons, L.L.C.
Brand DiscriptionOPDIVO is a sterile, preservative-free, non-pyrogenic, clear to opalescent, colorless to pale-yellow liquid that may contain light (few) particles. OPDIVO injection for intravenous infusion is supplied in single-dose vials.
Prescribed forOPDIVO® (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 NameNA
Formulationsolution
Physcial AppearnceLiquid
Route of AdministrationIntravenous
Recommended DosageThe 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.
ContraindicationNA
Side EffectsImmune-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 Linkhttp://www.rxlist.com/opdivo-drug/side-effects-interactions.htm
PubMed ID25765457, 28318993, 28317087, 28314688, 28314298, 28306559, 28304223, 28303763, 28303522
3-D StructureTh1206 Heavy chianor (Download)Th1206 Light chian (View) or (Download)