Cosibelimab (Monograph)

Brand name: Unloxcyt
Drug class: Antineoplastic Agents

Introduction

Cosibelimab-ipdl, a programmed death ligand-1 (PD-L1) blocking antibody, is an antineoplastic agent.

Uses for Cosibelimab

Cosibelimab-ipdl has the following uses:

Cosibelimab-ipdl is indicated for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

Cosibelimab Dosage and Administration

General

Cosibelimab-ipdl is available in the following dosage form(s) and strength(s):

Injection: 300 mg/5 mL (60 mg/mL) solution in a single-dose vial for dilution.

Dosage

Adults

Dosage and Administration

• The recommended dosage of cosibelimab-ipdl is 1,200 mg administered as an IV infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

• Dilute commercially available injection solution prior to administration. Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter.

• Administer by IV infusion over 60 minutes through an IV line containing a sterile, in-line or add-on of 0.2-micron to 0.22-micron filter.

• Do not administer cosibelimab-ipdl as an IV push or bolus injection.

• Do not co-administer other drugs through the same infusion line.

• See Full Prescribing Information for additional information on preparation and administration, and for dosage modification recommendations for adverse reactions.

Cautions for Cosibelimab

Contraindications

None.

Warnings/Precautions

Severe and Fatal Immune-Mediated Adverse Reactions

Cosibelimab-ipdl is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed in WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated reactions.

Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue cosibelimab-ipdl depending on severity. In general, if cosibelimab-ipdl requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.

Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below in the following sections.

Immune-Mediated Pneumonitis

Cosibelimab-ipdl can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

Immune-mediated pneumonitis occurred in 1% (3/223, Grade 2) of patients receiving cosibelimab-ipdl. Pneumonitis led to withholding of therapy in 0.4% (1/223) of patients. All 3 patients required systemic corticosteroids and pneumonitis did not resolve. One patient in whom cosibelimab-ipdl was withheld for pneumonitis, had cosibelimab-ipdl reinitiated after symptom improvement and had recurrence of pneumonitis.

Immune-Mediated Colitis

Cosibelimab-ipdl can cause immune-mediated colitis, which may present with diarrhea, abdominal pain, and lower GI bleeding. Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated colitis occurred in 0.4% (1/223, Grade 1) of patients receiving cosibelimab-ipdl. Systemic corticosteroids were required in the patient experiencing colitis. The event of colitis did not resolve, and cosibelimab-ipdl was not reinitiated.

Immune-Mediated Hepatitis

Cosibelimab-ipdl can cause immune-mediated hepatitis, defined as requiring the use of systemic corticosteroids and the absence of a clear alternate etiology.

Immune-Mediated Endocrinopathies

Cosibelimab-ipdl can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue therapy depending on severity. Adrenal insufficiency occurred in 0.9% (2/223) of patients receiving cosibelimab-ipdl, including Grade 2 in 0.4% (1/223) of patients. Cosibelimab-ipdl was withheld for adrenal insufficiency in one of these patients and was reinitiated after symptom improvement. Systemic corticosteroids were required in both patients with adrenal insufficiency.

Cosibelimab-ipdl can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue therapy depending on severity.

Cosibelimab-ipdl can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue therapy depending on severity.

Hypothyroidism occurred in 10% (22/223) of patients receiving cosibelimab-ipdl, including Grade 2 in 5% (10/223) of patients. Hypothyroidism resolved in 7 of the 22 patients.

Hyperthyroidism occurred in 5% (12/223) of patients receiving cosibelimab-ipdl, including Grade 2 in 0.4% (1/223) of patients. Hyperthyroidism resolved in 10 of the 12 patients.

Cosibelimab-ipdl can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue therapy depending on severity.

Immune-Mediated Nephritis with Renal Dysfunction

Cosibelimab-ipdl can cause immune-mediated nephritis, defined as the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology.

Immune-Mediated Dermatologic Adverse Reactions

Cosibelimab-ipdl can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue cosibelimab-ipdl depending on severity.

Immune-mediated dermatologic adverse reactions occurred in 7% (15/223) of patients receiving cosibelimab-ipdl, including Grade 3 in 0.9% (2/223) of patients and Grade 2 in 4% (9/223) of patients. Dermatologic adverse reactions led to permanent discontinuation of cosibelimab-ipdl in 0.4% (1/223) of patients and withholding of therapy in 0.9% (2/223) of patients. Systemic corticosteroids were required in 33% (5/15) of patients with dermatologic adverse reactions. Dermatologic adverse reactions resolved in 7 of the 15 patients. Of the 2 patients in whom cosibelimab-ipdl was withheld for dermatologic adverse reactions, 1 patient reinitiated cosibelimab-ipdl after symptom improvement and had recurrence of the dermatologic adverse reaction, which resolved after the drug was withheld a second time.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred in <1% of the 223 patients who received cosibelimab-ipdl or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

Cardiac/Vascular: Myocarditis, pericarditis, vasculitis.

Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy.

Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis.

Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.

Endocrine: Hypoparathyroidism.

Other (Hematologic/Immune): Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Infusion-related Reactions

Cosibelimab-ipdl can cause severe or life-threatening infusion-related reactions. Infusion-related infusion reactions were reported in 11% (24/223) of patients, including Grade 2 in 5.8% (13/223) of patients receiving cosibelimab-ipdl.

Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue therapy based on severity of the reaction. Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to infusions of therapeutic proteins.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action, cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with cosibelimab-ipdl and for 4 months after the last dose.

Specific Populations

Pregnancy

Based on its mechanism of action, cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman. There are no available data on the use of cosibelimab-ipdl in pregnant women. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Human IgG1 immunoglobulins (IgG1) are known to cross the placental barrier; therefore, cosibelimab-ipdl has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There is no information regarding the presence of cosibelimab-ipdl in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose.

Females and Males of Reproductive Potential

Cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman.

Pediatric Use

The safety and effectiveness of cosibelimab-ipdl have not been established in pediatric patients.

Geriatric Use

Of the 141 patients treated with cosibelimab-ipdl as a single agent, 21% (29) were younger than 65 years of age, 31% (44) were 65 through 75 years of age, and 48% (68) were 75 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Common Adverse Effects

The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments.

Please see product labeling for drug interaction information.

Actions

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. Cosibelimab-ipdl binds PD-L1 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 anti-tumor immune response. Cosibelimab-ipdl has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

• Advise patients that cosibelimab-ipdl can cause immune-mediated adverse reactions that may require corticosteroid treatment and interruption or discontinuation of therapy; such reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic adverse reactions, and other immune-mediated adverse reactions.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of pneumonitis, including new or worsening symptoms of cough, chest pain, or shortness of breath.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of colitis, including diarrhea, blood or mucus in stools, or severe abdominal pain.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatitis.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis.

• Advise patients to contact their healthcare provider immediately if they develop a new rash.

• Advise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms.

• Advise patients of the risk of solid organ transplant rejection and other transplant (including corneal graft) rejection. Advise patients to contact their healthcare provider immediately for signs or symptoms of organ transplant (including corneal graft) rejection.

• Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions.

• Advise patients to contact their healthcare provider immediately if they develop signs or symptoms of post-allogeneic HSCT complications or of solid organ transplant rejections.

• Advise females of reproductive potential that cosibelimab-ipdl can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy.

• Advise females of reproductive potential to use effective contraception during treatment with cosibelimab-ipdl and for 4 months after the last dose.

• Advise female patients not to breastfeed during treatment with cosibelimab-ipdl and for 4 months after the last dose.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Cosibelimab Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for cosibelimab.

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