Nivolumab
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Nivolumab, sold under the
brand name A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...
Opdivo, is an
anti-cancer medication Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a cu ...
in the class of immune checkpoint inhibitors. It selectively binds and blocks the programmed death-1 (PD-1) receptor on
T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
, thereby facilitating their activation. It is used to treat a number of types of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. This includes
melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
,
lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
,
malignant pleural mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...
,
renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the Proximal tubule, proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cance ...
,
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...
,
head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...
,
urothelial carcinoma Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and ...
,
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
,
esophageal squamous cell carcinoma Esophageal can refer to: * The esophagus * Esophageal arteries * Esophageal glands * Esophageal cancer Esophageal cancer (American English) or oesophageal cancer (British English) is cancer arising from the esophagus—the food pipe that run ...
,
liver cancer Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondar ...
,
gastric cancer Stomach cancer, also known as gastric cancer, is a malignant tumor of the stomach. It is a cancer that develops in the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes ...
, and esophageal or gastroesophageal junction cancer. It is administered
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
ly. The most common side effects include fatigue, rash, musculoskeletal pain,
pruritus An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
(itching), diarrhea, nausea,
asthenia Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...
(weakness), cough,
dyspnea Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that ...
(shortness of breath), constipation, decreased appetite, back pain,
arthralgia Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceuti ...
(joint pain), upper respiratory tract infection,
pyrexia Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...
(fever), headache, abdominal pain, and vomiting. Use during pregnancy may harm the baby. Nivolumab is a human
IgG4 Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...
that blocks PD-1. It is a type of
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
and works as a
checkpoint inhibitor Checkpoint inhibitor therapy is a form of Treatment of cancer, cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some ca ...
, blocking a signal that prevents activation of
T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
from attacking the cancer. The most common side effects when used in combination with chemotherapy include peripheral neuropathy (damage to the nerves outside of the brain and spinal cord), nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation and musculoskeletal pain. Nivolumab was approved for medical use in the United States in 2014. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. It is made using
Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are a family of immortalized cell lines derived from epithelial cells of the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therap ...
s. Nivolumab is the second FDA-approved systemic therapy for mesothelioma and is the first FDA-approved immunotherapy for the first-line treatment of gastric cancer.


Medical uses

In the US, nivolumab is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
to treat: Nivolumab is used as a first-line treatment for inoperable or
metastatic melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
in combination with
ipilimumab Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recogniz ...
if the cancer does not have a mutation in BRAF, and as a second-line treatment for inoperable or metastatic melanoma following treatment with ipilimumab and, if the cancer has a BRAF mutation, a
BRAF inhibitor ''BRAF'' is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Ra ...
. It is also used to treat metastatic squamous
non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...
with progression with or after platinum-based drugs, and for treatment of
small cell lung cancer Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr ...
. It also used as a second-line treatment for
renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the Proximal tubule, proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cance ...
after
anti-angiogenic An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...
treatment has failed. Nivolumab is used for primary or metastatic
urothelial carcinoma Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and ...
, the most common form of
bladder cancer Bladder cancer is the abnormal growth of cells in the bladder. These cells can grow to form a tumor, which eventually spreads, damaging the bladder and other organs. Most people with bladder cancer are diagnosed after noticing blood in thei ...
. It can be used for locally advanced or metastatic disease that progresses during or following
platinum-based chemotherapy Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemothe ...
or progresses within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy. Nivolumab is indicated for the adjuvant treatment of melanoma with lymph node involvement as well as in metastatic disease with previous complete resection. The combination of nivolumab with ipilimumab is used for the first-line treatment of adults with inoperable
malignant pleural mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...
. In April 2021, the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approved nivolumab, in combination with certain types of chemotherapy, for the initial treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. In May 2021, the FDA approved nivolumab for the treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease after neoadjuvant
chemoradiotherapy Chemoradiotherapy (CRT, CRTx, CT-RT) is the combination of chemotherapy and radiotherapy to treat cancer. Synonyms include radiochemotherapy (RCT, RCTx, RT-CT) and chemoradiation. It is a type of multimodal cancer therapy. Chemoradiation can be ' ...
. In August 2021, the FDA approved nivolumab for the adjuvant treatment of urothelial carcinoma who are at high risk of recurrence after undergoing radical resection. In May 2022, the FDA expanded the indication to include the first-line treatment of people with advanced or metastatic esophageal squamous cell carcinoma. In the same year, the FDA approved a combination therapy consisting of
relatlimab Relatlimab is a monoclonal antibody designed for the treatment of melanoma. It is used in combination with nivolumab to treat melanoma. Relatlimab is a Lymphocyte activation gene-3 (LAG-3) inhibitor. It is under development by Bristol-Myers Squ ...
and nivolumab for the treatment of some cases of advanced melanoma. In March 2024, the FDA approved nivolumab, in combination with
cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
and
gemcitabine Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...
, as a first-line treatment for adults with unresectable or metastatic
urothelial carcinoma Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and ...
. In October 2024, the FDA approved nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In April 2025, the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
approved Nivolumab with
Ipilimumab Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recogniz ...
(Yervoy,
Bristol Myers Squibb The Bristol-Myers Squibb Company, Trade name, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies ...
) for the treatment of adults and children aged 12 years and older with certain types of colorectal cancer.


Side effects

The US FDA prescription label contains warnings regarding increased risk for severe immune-mediated inflammation of the lungs, colon,
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, and
kidneys In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
(with accompanying kidney dysfunction), as well as immune-mediated
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
and
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
. Hypothyroidism and hyperthyroidism may affect 8.5% and 3.7% of patients, respectively. Autoimmune diabetes similar to
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...
may occur in approximately 2% of people treated with nivolumab. In trials for melanoma, the following side effects occurred in more than 10% of subjects and more frequently than with chemotherapy alone: rash and itchy skin, cough, upper respiratory tract infections, and peripheral edema. Other clinically important side effects with less than 10% frequency were ventricular arrhythmia, inflammation of parts of the eye (
iridocyclitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and i ...
), infusion-related reactions, dizziness, peripheral and sensory
neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
, peeling skin,
erythema multiforme Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands. It is typically associated with infection ...
,
vitiligo Vitiligo (, ) is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure, and susceptibili ...
, and
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
. In trials for lung cancer, the following side effects occurred in more than 10% of subjects and more frequently than with chemotherapy alone: fatigue, weakness, edema, fever, chest pain, generalized pain, shortness of breath, cough, muscle and joint pain, decreased appetite, abdominal pain, nausea and vomiting, constipation, weight loss, rash, and itchy skin. Levels of electrolytes and blood cells counts were also disrupted.


Pregnancy and breastfeeding

Use during pregnancy may harm the baby.


Pharmacokinetics

Based on data from 909 patients, the
terminal half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
of nivolumab is 26.7 days and steady-state concentrations were reached by 12 weeks when administered at 3 mg/kg every two weeks. Age, gender, race, baseline LDH,
PD-L1 Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the ''CD274'' gene. Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane prote ...
expression, tumor type, tumor size, renal impairment, and mild hepatic impairment do not affect clearance of the drug.


Mechanism of action

Nivolumab's mechanism of action is based on its role as a monoclonal antibody that selectively binds to the programmed death-1 (PD-1) receptor on the surface of
T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
, a type of
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
that plays a crucial role in the immune system’s ability to combat malignancies. Normally, certain cancer cells exploit the PD-1 pathway to shield themselves from the immune response by expressing programmed death-ligand 1 (PD-L1), which interacts with the PD-1 receptor and inhibits T-cell activation and proliferation. Nivolumab interrupts this interaction by binding to the PD-1 receptor, thereby blocking tumor cells from evading immune detection. This blockade enhances T-cell response, boosts the immune system's anti-tumor activity, and ultimately contributes to the destruction of cancer cells. PD-1 is a protein located on the surface of T cells that have been activated in the body's immune response. Normally, the immune system is controlled in part by certain molecules, such as PD-L1 or PD-L2, which can bind to PD-1. When they do, they prevent the T cell from taking action, which helps to ensure the body does not have an excessive immune reaction. However, many cancer cells take advantage of this system by producing PD-L1 themselves, effectively shutting down T cells and protecting the tumor from an immune attack. Nivolumab interferes with this process—it attaches to PD-1 and prevents PD-L1 from binding to it, which frees the T cells to target and destroy the tumor. Approximately 40–50% of melanoma cells express PD-L1. Aside from this, PD-L1 is not commonly found in the body, though it is present in certain areas such as the lining of the respiratory tract and in placental tissue.


Physical properties

Nivolumab is a fully human monoclonal
immunoglobulin G4 Ig gamma-4 chain C region is a protein that in humans is encoded by the ''IGHG4'' gene. See also * Immunoglobulin heavy chain (IGH) * Immunoglobulin G Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antib ...
antibody to
PD-1 Programmed cell death protein 1 (PD-1), (CD279 cluster of differentiation 279). PD-1 is a protein encoded in humans by the ''PDCD1'' gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's re ...
. The gamma 1 heavy chain is 91.8% unmodified human design while the kappa light chain is 98.9%.WHO Drug Information, Vol. 26, No. 2, 2012
Proposed INN List 107
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History

It was invented at Medarex through a research collaboration with
Ono Pharmaceutical is one of the largest pharmaceutical companies in Japan. It is headquartered in Chuo-ku, Osaka, Japan, with its major plants in Higashinari-ku, Osaka, and Fujinomiya, Shizuoka., and its central research institute at Minase, Shimamoto-cho, Mi ...
. Under the agreement between the companies in 2005, Medarex held an exclusive right of nivolumab in North America, and Ono Pharmaceutical retained the right in all other countries except North America.
Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...
acquired Medarex in 2009, for $2.4B. Ono received approval from Japanese regulatory authorities to use nivolumab to treat unresectable melanoma in July 2014, which was the first regulatory approval of a PD-1 inhibitor. Nivolumab received US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approval for the treatment of melanoma in December 2014. In April 2015, the
Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...
of the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) recommended approval of nivolumab for metastatic melanoma as a monotherapy. In March 2015, the FDA approved it for the treatment of squamous cell lung cancer. In June 2015, the EMA granted a marketing authorization valid throughout the European Union. In November 2015, the FDA approved nivolumab as a second-line treatment for
renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the Proximal tubule, proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cance ...
after having granted the application
breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...
designation,
fast track Fast Track, Fast track, or Fasttrack may refer to: Processes and systems * Fast track (FDA), a U.S. Food and Drug Administration expedited review program * Fast track (trade), the authority of the U.S. President to broker trade agreements with lim ...
designation, and
priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...
status. In May 2016, the FDA approved nivolumab for the treatment of people with classical Hodgkin lymphoma who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation
brentuximab vedotin Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymph ...
. In December 2017, the FDA granted approval to nivolumab for adjuvant treatment of melanoma with involvement of lymph nodes or for metastatic disease with complete resection. In April 2018, the FDA granted approval to nivolumab in combination with
ipilimumab Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recogniz ...
for the first-line treatment of people with intermediate and poor risk advanced
renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the Proximal tubule, proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cance ...
. In June 2018, China's Drug Administration approved nivolumab, the country's first immuno-oncology and the first PD-1 therapy. In October 2020, the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approved the combination of nivolumab with ipilimumab for the first-line treatment of adults with malignant pleural mesothelioma (MPM) that cannot be removed by surgery. In April 2021, the FDA approved nivolumab, in combination with certain types of chemotherapy, for the initial treatment of people with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma. In March 2024, the FDA approved nivolumab, in combination with cisplatin and gemcitabine, for first-line treatment of adults with unresectable or metastatic urothelial carcinoma. Efficacy was evaluated in CHECKMATE-901 (NCT03036098), a randomized, open-label trial enrolling 608 participants with previously untreated unresectable or metastatic urothelial carcinoma. Participants were randomized (1:1) to receive either nivolumab in combination with cisplatin and gemcitabine (up to six cycles) followed by nivolumab alone for up to two years or cisplatin and gemcitabine (up to six cycles). On both arms, participants discontinuing cisplatin were permitted to receive carboplatin. Randomization was stratified by tumor PD-L1 expression and presence of liver metastasis.


Research

Nivolumab, and other PD-1 inhibitors, appear to be effective in people with brain metastases and for cancer in people with autoimmune diseases.


Hodgkin's lymphoma

In
Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...
,
Reed–Sternberg cell Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are distinctive, giant cells found with light microscopy in biopsies from individuals with Hodgkin lymphoma. They are usually derived from B lymphocytes, classicall ...
s harbor amplification of
chromosome 9 Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome, as they normally do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of DN ...
p24.1, which encodes PD-L1 and PD-L2, and leads to their constitutive expression. In a small clinical study published in 2015, nivolumab elicited an objective response in 87% of a cohort of 20 patients. The evidence for a favorable effect of nivolumab on overall survival, quality of life, progression-free survival, and complete response among individuals with Hodgkin's lymphoma is uncertain.


Biomarkers

Amplification of chromosome 9p24 may serve as a predictive biomarker in Hodgkin's lymphoma. Every manufacturer pursuing drug development using monoclonal antibodies against PD-1 has developed assays to measure PD-L1 level as a potential biomarker using the antibody as the analyte-specific reagent. Bristol Myers Squibb partnered with Dako on a nivolumab-based assay. However, as of 2015 the complexity of the immune response had hindered efforts to identify people who would be likely to respond well to PD-1 inhibitors. PD-L1 levels appeared to be dynamic and modulated by several factors, and efforts to correlate PD-L1 levels before or during treatment with treatment response or duration of response had failed to reveal any useful correlations as of 2015.


Lung cancer

In 2016, Bristol Myers Squibb announced the results of a clinical trial in which nivolumab failed to achieve its endpoint and was no better than traditional chemotherapy at treating newly diagnosed lung cancer. Bristol Myers Squibb went on to attempt to gain approval for a combination therapy for lung cancer that included nivolumab and the company's older drug ipilimumab. The application was withdrawn in early 2019 following disappointing results. Infusion durations of 60 minutes and 30 minutes appear to have similar pharmacokinetics (absorption, distribution, metabolism, and elimination). Nivolumab is indicated for the treatment of people with metastatic squamous
non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...
with progression on or after platinum-based chemotherapy. CHECKMATE-227 tested the combination of nivolumab and ipilimumab in participants with stage IV or recurrent non-small cell lung cancer without previous treatment. Participants with a PD-L1 expression level of 1% or more were randomized in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or standard chemotherapy. The chemotherapeutics used were
cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
or
carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...
combined with
gemcitabine Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...
for people with squamous-cell non-small cell lung cancer, or pemetrexed for those with nonsquamous disease. The overall survival was 17.1, 15.7, and 14.9 months, respectively. The participants who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. The overall survival among that group was 17.2, 15.2 and 12.2 months, respectively. In June 2023, Bristol Myers Squibb provided positive four-year follow-up results from a phase III study (CheckMate-9LA) of a combination of nivolumab and ipilimumab along with chemotherapy, compared to chemotherapy alone, as first-line treatment in people with metastatic non-small cell lung cancer. The trial found an overall survival of 21% at a median follow-up of 47.9 months among those treated with the dual immunotherapy-based combination compared to 16% of participants treated with chemotherapy alone.


Melanoma

PD-L1 is expressed in 40-50% of melanomas. Phase I and II clinical trials have shown nivolumab as a promising and durable treatment option in melanoma as a single agent and in combination with ipilimumab. Phase III trials are ongoing. In October 2022, the results of a phase III trial, CheckMate -76K, showed that Opdivo reduced the risk of death by 58% as an adjuvant therapy in participants with completely resected stage two melanoma, the most serious type of skin cancer.


Urothelial carcinoma

In February 2023, Bristol Myers Squibb reported that the three-year follow-up results from its phase III (CheckMate-274) trial of nivolumab showed significant sustained clinical benefits with nivolumab for the adjuvant treatment of participants with muscle-invasive urothelial carcinoma at a high risk of recurrence after radical resection.


See also

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Nivolumab/relatlimab Nivolumab/relatlimab, sold under the brand name Opdualag, is a fixed-dose combination medication use to treat melanoma. It contains nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation ge ...


References


External links

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