Nivolumab

Identification

Summary

Nivolumab is a PD-1 blocking antibody used to treat melanoma, non small-cell lung cancer, renal cell cancer, head and neck cancer, and Hodgkin lymphoma.

Brand Names

Opdivo, Opdualag

Generic Name

Nivolumab

DrugBank Accession Number

DB09035

Background

Nivolumab is a fully human IgG4 antibody targeting the immune checkpoint programmed death receptor-1 (PD-1).⁶ This antibody was produced entirely in mice and grafted onto human kappa and IgG4 Fc region with the mutation S228P for additional stability and reduced variability.⁵ It was developed by Bristol Myers Squibb.⁶

Nivolumab was granted FDA approval on 22 December 2014.⁶ It is also available in combination with relatlimab under the brand name Opdualag.^11,13,14

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Structure

Protein Chemical Formula: C₆₃₆₂H₉₈₆₂N₁₇₁₂O₁₉₉₅S₄₂
Protein Average Weight: 143597.3811 Da

Sequences

>Heavy Chain Sequence
QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY
ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS
VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS
VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT
VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV
MHEALHNHYTQKSLSLSLGK

>Light Chain Sequence
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Download FASTA Format

Synonyms

Nivolumab

External IDs

BMS 936558
BMS-936558
GTPL7335
MDX 1106
MDX-1106
ONO 4538
ONO-4538

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Pharmacology

Indication

Nivolumab is indicated to treat unresectable or metastatic melanoma, melanoma as adjuvant treatment, resectable or metastatic non-small cell lung cancer, small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, hepatocellular carcinoma, and esophageal cancer.^6,9 The indication for classical Hodgkin lymphoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, and hepatocellular carcinoma were approved under accelerated approval based on the overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.⁶

Nivolumab is also approved for the treatment of HER2-negative advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma when used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen.⁸

In combination with relatlimab, nivolumab is indicated for the treatment of patients ≥12 years old with unresectable or metastatic melanoma.^11,13,14

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Associated Conditions

Indication Type	Indication	Approval Level	Age Group	Dose Form
Used in combination to treat	Advanced esophageal adenocarcinoma	••••••••••••	•••••	•••••••••
Used as adjunct in combination to treat	Advanced esophageal adenocarcinoma	••••••••••••	•••••	•••••••••
Used as adjunct in combination to treat	Advanced esophageal adenocarcinoma	••••••••••••		•••••••••
Used in combination to treat	Advanced gastric adenocarcinoma	••••••••••••	•••••	•••••••••
Used as adjunct in combination to treat	Advanced gastric adenocarcinoma	••••••••••••	•••••	•••••••••

Associated Therapies

Contraindications & Blackbox Warnings

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Pharmacodynamics

Nivolumab blocks PD-1 inhibitory signalling to T-cells.⁶ It has a long duration of action as it is administered every 2-4 weeks.⁶ Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion-related adverse effects, complications of allogenic hematopoietic stem cell transplants, embryo-fetal toxicity.⁶

Mechanism of action

The ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells.⁶ Tumor cells express PD-L1 and PD-L2.⁶ Nivolumab binds to PD-1, preventing PD-L1 and PD-L2 from inhibiting the action of T-cells, restoring a patient's tumor-specific T-cell response.¹

Target	Actions	Organism
AProgrammed cell death protein 1	inhibitor antibody	Humans
UProgrammed cell death 1 ligand 1	inhibitor antibody	Humans

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.¹ 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*h/mL respectively.³

Volume of distribution

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.³ At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L.⁴

Protein binding

There is no information regarding the plasma protein binding of nivolumab.⁷

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.⁷

Route of elimination

There have not been studies regarding the specific route of elimination of nivolumab.⁷

Half-life

The serum half life of nivolumab is approximately 20 days¹ with an elimination half life of 26.7 days.⁴

Clearance

The estimated clearance rate of nivolumab is 9.4 mL/h.² The clearance rate seems to be increased according to body weight.⁴

Adverse Effects

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Toxicity

Data regarding overdoses of nivolumab are not readily available.⁶ Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema.⁶

Pathways

Not Available

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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Nivolumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Nivolumab.
Aducanumab	The risk or severity of adverse effects can be increased when Nivolumab is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Nivolumab.
Alirocumab	The risk or severity of adverse effects can be increased when Nivolumab is combined with Alirocumab.

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Nivolumab Bms	Injection, solution, concentrate	10 mg/ml	Intravenous	Bristol Myers Squibb Pharma Eeig	2021-01-12	2016-01-14
Nivolumab Bms	Injection, solution, concentrate	10 mg/ml	Intravenous	Bristol Myers Squibb Pharma Eeig	2021-01-12	2016-01-14
Opdivo	Injection	10 mg/1mL	Intravenous	E.R. Squibb & Sons, L.L.C.	2014-12-22	Not applicable
Opdivo	Injection, solution, concentrate	10 mg/ml	Intravenous	Bristol Myers Squibb Pharma Eeig	2022-05-04	Not applicable
Opdivo	Injection	10 mg/ml	Intravenous	Bristol Myers Squibb Pharma Eeig	2020-12-15	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Opdualag	Nivolumab (240 mg / 20 mL) + Relatlimab (80 mg / 20 mL)	Solution	Intravenous	Bristol Myers Squibb	Not applicable	Not applicable
Opdualag	Nivolumab (12 mg/1mL) + Relatlimab (4 mg/1mL)	Injection	Intravenous	E.R. Squibb & Sons, L.L.C.	2022-03-18	Not applicable
Opdualag	Nivolumab (12 mg/ml) + Relatlimab (4 mg/ml)	Injection, solution, concentrate	Intravenous	Bristol Myers Squibb Pharma Eeig	2022-12-02	Not applicable

Chemical Identifiers

UNII: 31YO63LBSN
CAS number: 946414-94-4

References

General References

Brahmer JR, Hammers H, Lipson EJ: Nivolumab: targeting PD-1 to bolster antitumor immunity. Future Oncol. 2015;11(9):1307-26. doi: 10.2217/fon.15.52. Epub 2015 Mar 23. [Article]
Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y: Model-Based Population Pharmacokinetic Analysis of Nivolumab in Patients With Solid Tumors. CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):58-66. doi: 10.1002/psp4.12143. Epub 2016 Dec 26. [Article]
Lee KW, Lee DH, Kang JH, Park JO, Kim SH, Hong YS, Kim ST, Oh DY, Bang YJ: Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors. Oncologist. 2018 Feb;23(2):155-e17. doi: 10.1634/theoncologist.2017-0528. Epub 2017 Nov 20. [Article]
Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [Article]
Mashima E, Inoue A, Sakuragi Y, Yamaguchi T, Sasaki N, Hara Y, Omoto D, Ohmori S, Haruyama S, Sawada Y, Yoshioka M, Nishio D, Nakamura M: Nivolumab in the treatment of malignant melanoma: review of the literature. Onco Targets Ther. 2015 Aug 6;8:2045-51. doi: 10.2147/OTT.S62102. eCollection 2015. [Article]
FDA Approved Drug Products: Opdivo (nivolumab) for intravenous injection [Link]
BC Cancer Agency: Opdivo Monograph [Link]
Health Canada Product Monograph: Opdivo (nivolumab) for intravenous injection [Link]
Health Canada Approved Drug Products: OPDIVO (nivolumab) injection for Intravenous Infusion (August 2022) [Link]
EMA Approved Drug Products: OPDIVO (Nivolumab) solution, for intravenous injection [Link]
FDA Approved Drug Products: Opdualag (nivolumab and relatlimab-rmbw) injection for intravenous use [Link]
FDA Approved Drug Products: OPDIVO (nivolumab) injection, for intravenous use (October 2023) [Link]
EMA EPAR: Opdualag (relatlimab/nivolumab) [Link]
Health Canada Product Monograph: Opdualag (nivolumab and relatlimab) solution for intravenous injection [Link]

External Links

KEGG Drug: D10316
PubChem Substance: 347910393
RxNav: 1597876
ChEMBL: CHEMBL2108738
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Nivolumab

FDA label

Download (2.51 MB)

MSDS

Download (1.26 MB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Renal Neoplasms	1
4	Completed	Other	Renal Cell Carcinoma (RCC)	1
4	Completed	Treatment	Liver Cancer	1
4	Completed	Treatment	Lung Cancer	1
4	Completed	Treatment	Non-Small Cell Lung Cancer (NSCLC) / Non-Small Cell Lung Carcinoma / Renal Cancer / Renal Neoplasms	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution, concentrate	Intravenous	10 MG/ML
Injection	Intravenous	10 mg/1mL
Injection	Intravenous	10 mg/ml
Injection, solution, concentrate	Intravenous; Parenteral	10 MG/ML
Solution	Intravenous	10 mg / mL
Solution	Intravenous	100.000 mg
Solution	Intravenous	100 mg/10ml
Injection, solution	Intravenous
Solution	Intravenous	40 mg/4ml
Solution	Intravenous drip	10 mg/mL
Solution	Intravenous	40 mg
Solution	Intravenous	100 mg
Injection	Intravenous
Injection, solution, concentrate	Intravenous
Solution	Intravenous
Injection, solution, concentrate	Intravenous	10 mg/1ml

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US2013173223	No	2013-05-13	2033-05-13

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	80-90 ºC (based on IgG properties)	McConnell A., et al. (2014). MAbs. Sep-Oct; 6 (5); 1274-1282
boiling point (°C)	Fab and Fc domains denaturates at 60 and 70 ºC respectively	Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility	50 mg/ml	Human IgG purified. Product Information
isoelectric point	6.1-8.5	Agrisera Information about IgG antibodies.

Targets

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insights and accelerate drug research.

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Details1. Programmed cell death protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor
Antibody

General Function: Signal transducer activity
Specific Function: Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. ...
Gene Name: PDCD1
Uniprot ID: Q15116
Uniprot Name: Programmed cell death protein 1
Molecular Weight: 31646.635 Da

References

Taneja SS: Re: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. J Urol. 2012 Dec;188(6):2149. [Article]
Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]

Details2. Programmed cell death 1 ligand 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Antibody

General Function: Not Available
Specific Function: Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell ...
Gene Name: CD274
Uniprot ID: Q9NZQ7
Uniprot Name: Programmed cell death 1 ligand 1
Molecular Weight: 33275.095 Da

References

Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]

Drug created at February 24, 2015 23:02 / Updated at February 14, 2024 00:55

Nivolumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References