Cosibelimab: Drug information

For additional information see "Cosibelimab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Pharmacologic Category

Antineoplastic Agent, Anti-PD-L1 Monoclonal Antibody;
Antineoplastic Agent, Immune Checkpoint Inhibitor;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Cutaneous squamous cell carcinoma, metastatic or locally advanced

Cutaneous squamous cell carcinoma, metastatic or locally advanced: IV: 1,200 mg once every 3 weeks; continue until disease progression or unacceptable toxicity.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Altered kidney function prior to treatment initiation:

CrCl ≥15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in cosibelimab pharmacokinetics were observed.

CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

Acute kidney toxicity during treatment:

Immune-mediated nephritis with kidney dysfunction: If cosibelimab requires treatment interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to grade 1 or lower, then follow with a corticosteroid taper (continue to taper over at least 1 month). Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy.

Grade 2 or 3 increased SCr: Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4 increased SCr: Permanently discontinue cosibelimab.

Dosing: Liver Impairment: Adult

Liver impairment prior to treatment initiation:

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.

Severe (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (effect on cosibelimab pharmacokinetics is unknown).

Acute hepatotoxicity during treatment: If cosibelimab requires treatment interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to grade 1 or lower, then follow with a corticosteroid taper (continue to taper over at least 1 month). Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy.

Immune-mediated hepatitis WITHOUT tumor involvement of the liver:

ALT or AST >3 to 8 times ULN or total bilirubin >1.5 to 3 times ULN: Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

ALT or AST >8 times ULN or total bilirubin >3 times ULN: Permanently discontinue cosibelimab.

Immune-mediated hepatitis WITH tumor involvement of the liver:

Baseline ALT or AST >1 to 3 times ULN and increases to >5 to 10 times ULN or baseline ALT or AST >3 to 5 times ULN and increases to >8 to 10 times ULN:

Note: If ALT and AST are ≤ ULN at baseline, withhold or permanently discontinue cosibelimab based on recommendations for hepatitis without liver involvement.

Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

ALT or AST >10 times ULN or total bilirubin >3 times ULN: Permanently discontinue cosibelimab.

Additional recommendations:

Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).

Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m²experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: No dose reduction for cosibelimab is recommended.

Immune-mediated toxicities (general information):

Withhold cosibelimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue cosibelimab for life-threatening (grade 4) adverse reactions, recurrent severe (grade 3) adverse reactions that require systemic immunosuppressive treatment, or inability to reduce corticosteroid dose to ≤10 mg/day prednisone (or equivalent) within 12 weeks of corticosteroid initiation. If cosibelimab requires treatment interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to grade 1 or lower, then follow with a corticosteroid taper (continue to taper over at least 1 month). If immune-mediated adverse reaction is not controlled with systemic corticosteroids, consider administration of other systemic immunosuppressants. Systemic corticosteroids may not be necessary for certain adverse reactions. See table for additional dosage modification guidance.

Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

**Cosibelimab Recommended Dosage Modifications for Adverse Reactions**
Adverse reaction	Severity	Cosibelimab dosage modification
^a SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.
^b Refer to Prednisone (or equivalent) monograph for tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy.
Immune-mediated adverse reactions
Cardiovascular toxicity: Myocarditis	Grade 2, 3, or 4	Permanently discontinue cosibelimab.
Dermatologic toxicity	Mild to moderate nonbullous or nonexfoliative rash	May be managed with topical emollients and/or topical corticosteroids.
	Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESS^a	Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper^b. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
	Confirmed SJS, TEN, or DRESS^a	Permanently discontinue cosibelimab.
Endocrinopathies	Grade 2	Consider withholding cosibelimab until symptom improvement with hormone replacement; resume when acute symptoms have resolved.
	Grade 3 or 4	Withhold treatment until clinically stable or permanently discontinue cosibelimab depending on the severity. Resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper^b (if corticosteroids were indicated). Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
	Adrenal insufficiency, ≥ grade 2	Initiate symptomatic management (including hormone replacement as clinically indicated). Withhold or permanently discontinue cosibelimab depending on severity.
	Diabetes mellitus, type 1	Initiate insulin as clinically indicated. Withhold or permanently discontinue cosibelimab depending on severity.
	Hypophysitis	Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue cosibelimab depending on severity.
	Hyperthyroidism	Initiate medical management as clinically indicated. Withhold or permanently discontinue cosibelimab depending on severity.
	Hypothyroidism	Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue cosibelimab depending on severity.
GI adverse reactions: Colitis	Grade 2 or 3	Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper^b. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
GI adverse reactions: Colitis	Grade 4	Permanently discontinue cosibelimab.
Neurologic toxicities	Grade 2	Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper^b. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Neurologic toxicities	Grade 3 or 4	Permanently discontinue cosibelimab.
Ocular disorders: Vogt-Koyanagi-Harada-like syndrome	Any	May require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.
Pulmonary toxicity: Pneumonitis	Grade 2	Withhold cosibelimab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper^b. Permanently discontinue cosibelimab if no complete or partial resolution within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Pulmonary toxicity: Pneumonitis	Grade 3 or 4	Permanently discontinue cosibelimab.
Other adverse reactions
Infusion-related reactions	Grade 1 or 2	Interrupt or slow the rate of infusion.
Infusion-related reactions	Grade 3 or 4	Permanently discontinue cosibelimab.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and may include non–FDA-approved dosing or reports for other agents in this same pharmacological class (PD-1/PD-L1-blocking antibodies) and may not be specifically reported for cosibelimab.

>10%:

Cardiovascular: Edema (11%)

Dermatologic: Pruritus (12%), skin rash (23%)

Endocrine & metabolic: Decreased serum sodium (38%), hypothyroidism (14%), increased serum calcium (14%), increased serum potassium (23%)

Gastrointestinal: Constipation (13%), diarrhea (14%), increased serum lipase (25%), nausea (13%)

Hematologic & oncologic: Decreased hemoglobin (45%; grades 3/4: 4%), decreased platelet count (14%; grades 3/4: 1%), lymphocytopenia (41%; grades 3/4: 6%)

Hepatic: Increased serum alanine aminotransferase (25%), increased serum alkaline phosphatase (26%), increased serum aspartate aminotransferase (24%)

Immunologic: Antibody development (49%; neutralizing: 3%)

Nervous system: Fatigue (33%), headache (12%)

Neuromuscular & skeletal: Musculoskeletal pain (25%)

1% to 10%:

Genitourinary: Urinary tract infection (10%)

Hematologic & oncologic: Leukopenia (10%; grades 3/4: 1%)

Infection: Sepsis (3%)

Local: Localized infection (10%)

Respiratory: Pneumonia (serious: 3%)

Frequency not defined:

Cardiovascular: Myocarditis, pericarditis, thrombosis (tumor), vasculitis

Dermatologic: Dermatological reaction, pemphigoid

Endocrine & metabolic: Adrenocortical insufficiency, hyperthyroidism, hypoparathyroidism

Gastrointestinal: Cholestasis, colitis, duodenitis, gastritis, increased serum amylase, pancreatitis

Hematologic & oncologic: Aplastic anemia, hemolytic anemia (autoimmune), hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis]), wound hemorrhage

Hepatic: Hepatic cytolysis

Hypersensitivity: Infusion-related reaction

Immunologic: Organ transplant rejection (corneal graft, solid), sarcoidosis

Infection: Systemic inflammatory response syndrome

Nervous system: Demyelinating disease, encephalitis, Guillain- Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve), paresthesia

Neuromuscular & skeletal: Axillary pain, myelitis, myositis, neck pain, polymyositis, rhabdomyolysis

Ophthalmic: Corneal ulcer, eye pain, iritis, uveitis

Respiratory: Pneumonitis

Miscellaneous: Fever

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse events (immune mediated): PD-1/PD-L1 blockers (including cosibelimab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, may occur in any tissue or organ system and may affect more than one organ system simultaneously. Immune-mediated adverse reactions may occur at any time after initiating an anti-PD-L1/PD-1 monoclonal antibody. While immune-mediated adverse reactions generally manifest during treatment, they may also occur following cosibelimab discontinuation. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of anti-PD-1/PD-L1 monoclonal antibodies. If immune-mediated adverse reaction is suspected, initiate appropriate work-up to exclude alternate etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

• Dermatologic toxicity: Cosibelimab may cause immune-mediated rash or dermatitis. Grade 2 and 3 events have been reported. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have occurred with anti-PD-L1/PD-1 monoclonal antibodies. Systemic corticosteroids were required in one-third of patients with immune-mediated dermatologic adverse reactions. Dermatologic adverse reactions led to treatment interruption or permanent discontinuation in a small percentage of patients. Immune-mediated dermatologic adverse reactions resolved in approximately one-half of patients. Recurrence of dermatologic toxicity upon reinitiation of cosibelimab occurred but resolved following subsequent interruption.

• Endocrinopathies: Cosibelimab is associated with immune-mediated endocrinopathies.

- Adrenal insufficiency: Cosibelimab may cause primary or secondary adrenal insufficiency; grade 2 events have been reported. Treatment interruption was required in some cases, with reinitiation of treatment following symptom improvement; systemic corticosteroids were required in affected patients.

- Diabetes mellitus: Cosibelimab has been associated with the development of type 1 diabetes mellitus (which may present with diabetic ketoacidosis).

- Hypophysitis: Cosibelimab may cause immune-mediated hypophysitis. Hypophysitis may present with acute mass effect–associated symptoms such as headache, photophobia, or visual field cuts. Hypophysitis may cause hypopituitarism.

- Thyroid disorders: Cosibelimab may cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hyperthyroidism occurred in a small percentage of patients, including rare grade 2 events. Hyperthyroidism resolved in a majority of patients. Hypothyroidism may follow hyperthyroidism. Hypothyroidism also occurred in a small percentage of patients, including grade 2 events. Hypothyroidism resolved in approximately one-third of patients.

• GI adverse reactions: Cosibelimab may cause immune-mediated colitis; presenting signs/symptoms may include diarrhea, abdominal pain, and lower GI bleeding. Immune-mediated colitis occurred in a small percentage of patients. Systemic corticosteroids were required in patients who experienced colitis without resolution; cosibelimab was not rechallenged. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis who received anti-PD-L1/PD-1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatitis: Cosibelimab may cause immune-mediated hepatitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology.

• Infusion reactions: Severe or life-threatening infusion-related reactions have occurred in patients receiving cosibelimab, including grade 2 events.

• Nephrotoxicity: Cosibelimab may cause immune-mediated nephritis with kidney dysfunction, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology.

• Ocular disorders: Ocular events, including uveitis, iritis, and other ocular inflammatory toxicities have been reported; some cases may be associated with retinal detachment. Various grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.

• Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported rarely with cosibelimab or with other anti-PD-L1/PD-1 monoclonal antibodies (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitis, myositis/polymyositis, rhabdomyolysis (and associated sequelae including kidney failure), arthritis, polymyalgia rheumatica, hypoparathyroidism, autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), solid organ transplant rejection, and other transplant (including corneal graft) rejection.

• Pneumonitis: Cosibelimab may cause immune-mediated pneumonitis. In patients who received other anti-PD-L1/PD-1 monoclonal antibodies, the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Pneumonitis led to treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients who experienced pneumonitis without resolution. Recurrence of pneumonitis occurred among patients who reinitiated cosibelimab following symptom improvement.

Disease-related concerns:

• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic cell transplant (HCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and hematopoietic stem cell transplant. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogeneic HCT.

• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti-CTLA-4 with anti-PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and kidney and liver failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Product Availability

Unloxcyt: FDA approved December 2024; anticipated availability currently unknown.

Administration: Adult

IV: Infuse over 60 minutes through a sterile, 0.2- to 0.22-micron in-line or add-on filter; do not administer as an IV push or bolus. Do not administer other medications at the same time through the same IV line. If refrigerated, allow the diluted infusion solution to come to room temperature prior to administration.

Monitor for infusion-related reactions. Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions (consider premedication with an antipyretic and/or antihistamine for subsequent infusions); permanently discontinue for grade 3 or 4 infusion-related reactions.

Use: Labeled Indications

Cutaneous squamous cell carcinoma, metastatic or locally advanced:

Treatment of metastatic cutaneous squamous cell carcinoma (cSCC) in adults.

Treatment of locally advanced cSCC in adults who are not candidates for curative surgery or curative radiation.

Medication Safety Issues

Sound-alike/look-alike issues:

Cosibelimab may be confused with atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, tislelizumab, toripalimab, tremelimumab.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Antibiotics: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Corticosteroids (Systemic): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider Therapy Modification

Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase hepatotoxic effects of Ketoconazole (Systemic). Risk C: Monitor

Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Opioid Agonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Vitamin K Antagonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

Reproductive Considerations

Verify pregnancy status prior to use in patients who could become pregnant.

Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last dose of cosibelimab.

Pregnancy Considerations

Cosibelimab is a humanized monoclonal antibody (IgG₁). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action, in utero exposure to cosibelimab may disrupt maternal tolerance to the fetus, increasing the risk of abortion or stillbirth. Based on animal data, maternal use may also result in immune-mediated disorders in the newborn.

Breastfeeding Considerations

It is not known if cosibelimab is present in breast milk.

Cosibelimab is a humanized monoclonal antibody (IgG₁). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during therapy and for 4 months after the last dose of cosibelimab.

Monitoring Parameters

Evaluate hepatic function tests, SCr, and thyroid function tests (at baseline and periodically during treatment). Monitor blood glucose (for hyperglycemia). Verify pregnancy status prior to use in patients who could become pregnant.

Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, dermatologic toxicity, diabetes mellitus, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), hepatitis, hypophysitis, ocular disorders, pneumonitis, thyroid disorders, and other immune-mediated adverse reactions.

Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Additional suggested monitoring (ASCO [Schneider 2021]):

Prior to therapy: CBC with differential; creatine kinase; comprehensive clinical assessment including performance status, weight, BMI, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms.

During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections; screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks); CBC with differential; creatine kinase; monitor bone mineral density (with long-term therapy).

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term therapy (>12 months therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy) (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.

Mechanism of Action

Cosibelimab is a recombinant human IgG1 lambda monoclonal antibody which blocks PD-L1 binding to PD-1 and B7.1 receptors located on T-cells and antigen presenting cells. Normal PD-L1 binding to PD-1 and B7.1 receptors suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production. Inhibition of this interaction released the inhibitory effects of PD-L1 on the anti-tumor immune response (manufacturer's labeling). Cosibelimab has a fragment domain which induces antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity against tumor cells (Clingan 2023).

Pharmacokinetics (Adult Data Unless Noted)

Note: Cosibelimab steady state exposure at 1,200 mg every 3 weeks was comparable to exposure at 800 mg every 2 weeks in patients with cutaneous squamous cell carcinoma.

Distribution: V_dss: ~5.67 L.

Half-life elimination: 17.8 days.

Excretion: Clearance: 0.256 L/day.

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Unloxcyt (cosibelimab) [prescribing information). Waltham, MA: Checkpoint Therapeutics, Inc; December 2024.

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Cosibelimab: Drug information