Cosibelimab-ipdl, a human anti-programmed death ligand-1 (PD-L1) monoclonal antibody, is an antineoplastic agent.1
Cutaneous Squamous Cell Carcinoma
Cosibelimab-ipdl is used for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced cutaneous squamous cell carcinoma (laCSCC) who are not candidates for curative surgery or radiation.1
The safety and efficacy of cosibelimab-ipdl were principally established in a multicenter, multicohort, open-label study (Study CK-301-101) in adults with mCSCC or laCSCC who were not candidates for curative surgery or radiation.1 Patients were treated with cosibelimab-ipdl 800 mg IV every 2 weeks in 28-day cycles until disease progression or unacceptable toxicity.1, 3 Patients were excluded if they had active or suspected autoimmune disease, allogeneic transplant within 6 months prior to treatment, prior treatment with programmed cell death protein-1/programmed-death ligand-1 (PD-1)/PD-L1 monoclonal antibodies or other immune checkpoint inhibitor therapy, uncontrolled or significant cardiovascular disease, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, or infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.1 The primary efficacy endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by an independent central review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.1 For patients with laCSCC with externally visible target lesions not assessable by radiologic imaging, ORR was assessed by digital photography according to World Health Organization (WHO) criteria.1 Of the 109 patients included in the efficacy population, 78 had mCSCC (Group 1) and 31 had laCSCC (Group 2).1, 3 Additional supportive efficacy data were derived from 22 patients with mCSCC in Group 1 that were subsequently treated with cosibelimab-ipdl 1200 mg IV every 3 weeks.3 The median age of patients was 75 years (range: 37-95), and the majority were White (85%) and male (72%).1 Approximately 34% of patients had an ECOG PS of 0 and 66% had an ECOG PS of 1.1 The majority of patients had prior surgery (66%) or radiotherapy (69%), while 7% had received ≥1 prior anti-cancer systemic therapy.1
At the planned analysis date, the ORR was 50% in patients with mCSCC, with 10 complete responses and 29 partial responses.1, 4 The ORR in patients with laCSCC was 55%, with 8 complete responses and 9 partial responses.1 The 1200 mg every 3 weeks and 800 mg every 2 weeks dosages had similar ORR.3 DOR had not been reached for either group of patients at a median follow-up of 29.3 months in the mCSCC group and 24.1 months in the laCSCC group.1, 4
Cutaneous squamous cell carcinoma is the second most common skin cancer, with a rapidly increasing incidence due to aging of the world's population and increased exposure to ultraviolet radiation.2, 5 The majority of CSCCs are successfully treated with surgical excision, the standard of care for localized CSCC; however, some patients may progress to locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC).2, 5 Several PD-1-blocking antibodies (e.g., pembrolizumab, cemiplimab-rwlc, cosibelimab-ipdl) are available for the treatment of laCSCC or mCSCC in patients who are not candidates for surgery or radiation.1, 2 The American Academy of Dermatology's 2018 guideline for the management of CSCC describes surgical resection, adjuvant radiation therapy, and/or systemic chemotherapy as possible treatment strategies based on extent of disease; however, the PD-1-blocking antibodies indicated for the treatment of laCSCC and mCSCC were not mentioned in these guidelines, as they were approved after guideline publication.2, 5 Additional studies are needed to determine cosibelimab-ipdl's place of therapy in the treatment of laCSCC and mCSCC.2, 4, 5
Administer cosibelimab-ipdl via IV infusion.1
Cosibelimab-ipdl is available as a 300 mg/5 mL (60 mg/mL) injection solution that must be diluted prior to administration.1
Store vials of cosibelimab-ipdl in the refrigerator at 2-8°C in the original carton to protect from light.1 Do not freeze.1 Do not shake vials.1
Visually inspect each vial of cosibelimab-ipdl for particulate matter and discoloration.1 Discard the vial if visible particles are observed.1
Dilute cosibelimab-ipdl by adding 20 mL (1200 mg) of cosibelimab-ipdl injection (containing 60 mg/mL) to a 250 mL IV infusion bag containing 0.9% sodium chloride injection.1 Cosibelimab-ipdl is compatible with infusion bags made of polyolefin or polyvinyl chloride.1
Gently invert the solution to mix; do not shake.1
Discard any unused portion left in the vial.1
Store the prepared solution at room temperature (≤25°C) or in the refrigerator (2-8°C) for no more than 24 hours from the time of preparation until the end of infusion.1 Do not freeze.1 Discard after 24 hours.1
The prepared cosibelimab-ipdl solution is administered via IV infusion with an in-line or add-on 0.2-0.22-micron filter in a dedicated line over 1 hour.1 Do not administer as an IV push or bolus injection.1 Visually inspect the cosibelimab-ipdl infusion for particulate matter and discoloration prior to administration; discard if the solution is discolored or contains particulate matter.1
If refrigerated, bring the diluted solution to room temperature prior to administration.1
Administration rate may be modified for infusion-related reactions.1 If Grade 1 or 2 infusion-related reactions occur, interrupt or slow the rate of infusion.1 If Grade 3 or 4 infusion-related reactions occur, permanently discontinue cosibelimab-ipdl.1
Cutaneous Squamous Cell Carcinoma
The recommended adult dosage of cosibelimab-ipdl for the treatment of mCSCC or laCSCC in patients who are not candidates for curative surgery or radiation is 1200 mg administered via IV infusion over 60 minutes every 3 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity.1
Dosage Modification for Toxicity
No dosage reduction of cosibelimab-ipdl is recommended; however, if immune-mediated adverse reactions occur, temporary or permanent discontinuation of cosibelimab-ipdl may be required based on severity of the reaction.1
Adverse event severity is graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 5.1
In general, cosibelimab-ipdl should be temporarily withheld for severe (Grade 3) immune-mediated adverse reactions, and should be permanently discontinued for life-threatening (Grade 4) immune-mediate adverse reactions or recurrent severe (Grade 3) immune-mediated adverse reactions that require systemic immunosuppressive treatment.1 Cosibelimab-ipdl should also be permanently discontinued in patients unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating corticosteroid therapy.1
If Grade 2 pneumonitis occurs, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If Grade 3 or 4 pneumonitis occurs, permanently discontinue cosibelimab-ipdl.1
If Grade 2 or 3 immune-mediated colitis occurs, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If Grade 4 immune-mediated colitis occurs, permanently discontinue cosibelimab-ipdl.1
Immune-Mediated Hepatic Effects
In patients with immune-mediated hepatitis with no tumor involvement of the liver, if serum AST or ALT elevations increase >3 to ≤8 times the upper limit of normal (ULN) or total bilirubin increases to >1.5 to ≤3 times the ULN, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1 If AST or ALT increase to >8 times ULN or total bilirubin increases to >3 times ULN, permanently discontinue cosibelimab-ipdl.1
In patients with immune-mediated hepatitis with tumor involvement of the liver, if baseline AST or ALT is >1 to ≤3 times the ULN and increases to >5 to ≤10 times the ULN, or if baseline AST or ALT is >3 to ≤5 times the ULN and increases to >8 to ≤10 times the ULN, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1 If AST or ALT increases to >10 times the ULN or total bilirubin increases to >3 times the ULN, permanently discontinue cosibelimab-ipdl.1 If AST and ALT are less than or equal to the ULN at baseline in patients with liver involvement, withhold or permanently discontinue cosibelimab-ipdl based on recommendations for immune-mediated hepatitis with no tumor involvement of the liver.1
Immune-Mediated Endocrine Effects
If Grade 2 endocrinopathies occur, depending on clinical severity, consider withholding cosibelimab-ipdl until symptom improvement with hormone replacement.1 Resume once symptoms have resolved.1
If Grade 3 or 4 endocrinopathies occur, withhold cosibelimab-ipdl until clinically stable, or permanently discontinue, depending on severity.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If Grade 2 or 3 increased blood creatinine occurs, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If Grade 4 increased blood creatinine occurs, permanently discontinue cosibelimab-ipdl.1
Immune-Mediated Dermatologic Adverse Reactions
If SJS, TEN, or DRESS is suspected, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If confirmed SJS, TEN, or DRESS occurs, permanently discontinue cosibelimab-ipdl.1
Immune-Mediated Cardiac Effects
If Grade 2, 3, or 4 myocarditis occurs, permanently discontinue cosibelimab-ipdl.1
Immune-Mediated Neurologic Effects
If Grade 2 neurological toxicities occur, withhold cosibelimab-ipdl.1 Resume in patients with complete or partial resolution (Grade 0-1) after corticosteroid taper.1 Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiation.1
If Grade 3 or 4 neurological toxicities occur, permanently discontinue cosibelimab-ipdl.1
Other Immune-Mediated Adverse Effects
If Grade 1 or 2 infusion-related reactions occur, interrupt or slow the rate of infusion.1
If Grade 3 or 4 infusion-related reactions occur, permanently discontinue cosibelimab-ipdl.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Severe and Fatal Immune-Mediated Adverse Reactions
Cosibelimab-ipdl, a monoclonal antibody, is part of a class of drugs that bind to either the PD-1 or PD-L1, blocking the PD-1/PD-L1 pathway, which removes inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.1 Important immune mediated-adverse reactions listed in the prescribing information may not include all possible reactions that may occur during therapy.1
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, and can occur at any time after starting a PD-1/PD-L1-blocking antibody.1 While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, they may also manifest after discontinuation.1 Immune-mediated adverse reactions affecting more than one body system can occur simultaneously.1
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1-blocking antibodies.1 Monitor closely for signs and symptoms of clinical manifestations of underlying immune-mediated adverse reactions.1 Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment.1 If immune-mediated adverse reactions are suspected, initiate an appropriate workup to exclude alternative etiologies, including infection.1 Institute medical management promptly, including specialty consultation as appropriate.1
Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of the immune-mediated adverse reaction.1 Generally, if temporary interruption or discontinuation is necessary, administer systemic corticosteroids (1-2 mg/kg/day prednisone or equivalent) until toxicity improves to Grade 1 or less.1 Upon improvement to Grade 1 or less, corticosteroids should be tapered over at least 1 month.1 Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with systemic corticosteroids.1
Cosibelimab-ipdl may cause immune-mediated pneumonitis.1 In patients treated with other PD-1/PD-L1-blocking antibodies, incidence is higher in patients who have received prior thoracic radiation.1
In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 3 patients (1%) experienced immune-mediated pneumonitis (Grade 2).1 All 3 patients required systemic corticosteroids; pneumonitis did not resolve.1 Cosibelimab-ipdl was withheld due to pneumonitis in 1 patient (0.4%); therapy was reinitiated after symptom improvement and the patient experienced pneumonitis recurrence.1
Cosibelimab-ipdl may cause immune-mediated colitis, which may present as diarrhea, abdominal pain, and/or lower GI bleeding.1
In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 1 patient (0.4%) experienced immune-mediated colitis (Grade 1).1 The patient required systemic corticosteroids; colitis did not resolve.1 Cosibelimab-ipdl was not reinitiated.1
Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1-blocking antibodies.1 If corticosteroid-refractory colitis occurs, consider repeating an infectious workup to exclude alternative etiologies.1
Cosibelimab-ipdl may cause immune-mediated hepatitis, defined as requiring the use of systemic corticosteroids and the absence of a clear alternate etiology.1 If elevations in AST, ALT, or bilirubin concentrations occur, temporarily withhold or permanently discontinue based on severity.1
Immune-Mediated Endocrine Effects
Immune-mediated endocrinopathies, including primary or secondary adrenal insufficiency, hypophysitis, thyroid dysfunction (i.e., hyperthyroidism, hypothyroidism, thyroiditis), and diabetes mellitus, have occurred in patients receiving cosibelimab-ipdl.1
Adrenal Insufficiency : In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 2 patients (0.9%) experienced adrenal insufficiency (Grade 2 in 1 patient).1 Both patients required systemic corticosteroids.1 Cosibelimab-ipdl was withheld due to adrenal insufficiency in 1 patient (0.4%); therapy was reinitiated after symptom improvement.1
For Grade ≥2 adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormonal replacement as clinically indicated.1 Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of the adrenal insufficiency.1
Hypophysitis : Hypophysitis may present with acute symptoms associated with mass effect, such as headache, photophobia, or visual field cuts.1 Hypophysitis may cause hypopituitarism.1
If hypophysitis occurs, initiate hormone replacement as clinically indicated.1 Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of the hypophysitis.1
Thyroid Disorders : Thyroiditis may present with or without endocrinopathies.1 Hypothyroidism can follow hyperthyroidism.1 In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 22 patients (10%) experienced hypothyroidism, including Grade 2 in 10 patients (5%).1 Hypothyroidism resolved in 7 of the 22 patients.1 A total of 12 patients (5%) experienced hyperthyroidism, including Grade 2 in 1 patient (0.4%).1 Hyperthyroidism resolved in 10 of the 12 patients.1
If thyroid disorders occur, initiate hormone replacement or medical management as clinically indicated.1 Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of the thyroid disorder.1
Diabetes Mellitus and Diabetic Ketoacidosis : Diabetes mellitus may present with or without diabetic ketoacidosis.1
Monitor patients for hyperglycemia or other signs and symptoms of diabetes.1 Initiate treatment with insulin as clinically indicated.1 Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of diabetes.1
Cosibelimab-ipdl may cause immune-mediated nephritis, defined as the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology.1
Immune-Mediated Dermatologic Adverse Reactions
Cosibelimab-ipdl may cause immune-mediated rash or dermatitis.1 Bullous and exfoliative dermatitis, including SJS, TEN, and DRESS have occurred with PD-1/PD-L1-blocking antibodies.1
In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 15 patients (7%) experienced immune-mediated dermatologic adverse reactions, including Grade 3 in 2 patients (0.9%) and Grade 2 in 9 patients (4%).1 Systemic corticosteroids were required in 5 of the 15 patients; the dermatologic adverse reactions resolved in 7 of the 15 patients.1 Cosibelimab-ipdl was permanently discontinued in 1 patient (0.4%) and withheld in 2 patients (0.9%).1 Of the 2 patients in which cosibelimab-ipdl was withheld, 1 patient reinitiated treatment after symptom improvement and experienced recurrence, which resolved after cosibelimab-ipdl was withheld a second time.1
Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.1 Temporary interruption or permanent discontinuation of cosibelimab-ipdl may be necessary depending on the severity of the dermatologic adverse reactions.1
Other Immune-Mediated Adverse Reactions
Other clinically significant immune-mediated adverse reactions occurring at an incidence of <1%, which may be severe or fatal, have occurred in patients receiving cosibelimab-ipdl or receiving other PD-1/PD-L1 blocking antibodies.1
Cardiac/Vascular : Myocarditis, pericarditis, and vasculitis have been reported in patients treated with cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
Nervous system : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, and autoimmune neuropathy have occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
Ocular : Uveitis, iritis, and other ocular inflammatory toxicities have occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1 Some cases can be associated with retinal detachment.1 Various grades of visual impairment to blindness can occur.1 Diagnosis of a Vogt-Koyanagi-Harada-like syndrome should be considered in cases where uveitis occurs alongside other immune-mediated adverse reactions; this syndrome may require systemic corticosteroid treatment to reduce the risk of permanent vision loss.1
GI : Pancreatitis, including increases in serum amylase and lipase levels, gastritis, and duodenitis have occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
Musculoskeletal and Connective tissue : Myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, and polymyalgia rheumatica have occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
Endocrine : Hypoparathyroidism has occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
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, and other transplant (including corneal graft) rejection have occurred in patients receiving cosibelimab-ipdl or other PD-1/PD-L1 blocking antibodies.1
Severe or life-threatening infusion-related reactions may occur in patients receiving cosibelimab-ipdl.1 In a pooled safety analysis of 223 patients who received cosibelimab-ipdl, 24 patients (11%) experienced infused-related reactions, including Grade 2 in 13 patients (5.8%).1
Monitor patients for signs and symptoms of infusion-related reactions.1 Temporary interruption of the infusion, slower rate of administration, or permanent discontinuation of cosibelimab-ipdl may be necessary based on the severity of the reaction.1 Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to infusions of therapeutic proteins.1
Allogeneic Stem Cell Transplantation-Related Complications
Transplant-related complications, including 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), have occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to or following therapy with a PD-1/PD-L1 blocking antibody.1 Some cases have resulted in serious complications or death.1 Transplant-related complications following allogeneic HSCT may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.1
Monitor patients closely for evidence of transplant-related complications and intervene promptly.1 Prior to or after allogeneic HSCT, consider the benefits and risks of initiating treatment with a PD-1/PD-L1 blocking antibody.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman.1 In animal studies, blockade of the PD-1/PD-L1 pathway has demonstrated increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death.1
Advise pregnant women of the potential risk to a fetus.1 Verify pregnancy status in women of reproductive potential prior to initiation of cosibelimab-ipdl.1 Advise females of reproductive potential to use effective contraception during treatment with cosibelimab-ipdl and for 4 months after the last dose.1
Based on the mechanism of action, cosibelimab-ipdl may cause fetal harm when administered to a pregnant woman.1 There are no available human data on the use of cosibelimab-ipdl in pregnant women to evaluate a drug-associated risk.1
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.1
Human IgG1 immunoglobulins are known to cross the placental barrier; therefore, cosibelimab-ipdl has the potential to be transmitted from the mother to the developing fetus.1 Advise women of the potential risk to a fetus.1
Verify pregnancy status in women of reproductive potential prior to initiation of cosibelimab-ipdl.1
It is not known whether cosibelimab-ipdl is distributed into human milk.1 The effects of cosibelimab-ipdl on breastfed infants or on milk production are also unknown.1
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 of cosibelimab-ipdl.1
Females and Males of Reproductive Potential
Cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman.1
Verify pregnancy status in women of reproductive potential prior to initiation of cosibelimab-ipdl.1
Advise females of reproductive potential to use effective contraception during treatment with cosibelimab-ipdl and for 4 months after the last dose.1
Safety and efficacy of cosibelimab-ipdl have not been established in pediatric patients <18 years of age.1
In patients with laCSCC or mCSCC who received cosibelimab-ipdl, 31% were 65 through 75 years of age.1 No clinically meaningful differences in safety or efficacy were observed between older and younger patients (<65 years of age).1
The effects of severe hepatic impairment (bilirubin >3 times the upper limit of normal (ULN) and any AST) on the pharmacokinetics of cosibelimab-ipdl have not been studied.1
Renal impairment (creatinine clearance ≥15 mL/minute) does not have a clinically important effect on the pharmacokinetics of cosibelimab-ipdl; however, the effects of creatinine clearance <15 mL/minute on the pharmacokinetics of cosibelimab-ipdl have not been studied.1
The most common adverse reactions (incidence ≥10%) reported with cosibelimab-ipdl were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.1
Cosibelimab-ipdl, a humanized anti-programmed death ligand-1 (PD-L1) monoclonal antibody, is an antineoplastic agent.1 The drug is an IgG1 lambda monoclonal antibody.1
The immune-checkpoint receptor PD-1 is expressed on activated T-cells, monocytes, B-cells, natural killer (NK) T-cells, and dendritic cells.6, 7, 8, 9 Overexpression of PD-1 ligands on the surface of tumor cells results in activation of PD-1 and B7.1 and suppression of cytotoxic T-cell activity, T-cell proliferation, and cytokine production.8, 9 Cosibelimab-ipdl blocks the interaction between PD-L1 and the receptors PD-1 and B7.1, thus releasing the inhibitory effects of PD-L1 on the anti-tumor immune response.1 In vitro, cosibelimab-ipdl has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC).1
Cosibelimab-ipdl exhibits dose-proportional pharmacokinetics over the dosage range of 800-1200 mg following a single dose.1 Following repeated doses of cosibelimab-ipdl 1200 mg IV every 3 weeks, steady-state concentrations are reached by approximately 84 days.1 The elimination half-life of cosibelimab-ipdl is 18 days.1 Age (24.8-95 years), sex, race, ethnicity, anti-drug antibody status, albumin (22-51 g/L), tumor type, tumor diameter, and renal impairment (creatinine clearance ≥15 mL/minute) do not have clinically important effects on the pharmacokinetics of cosibelimab-ipdl.1 The effect of severe hepatic impairment (bilirubin >3 times ULN and any AST) on the pharmacokinetics of cosibelimab-ipdl is unknown.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Cosibelimab-ipdl is obtained through designated specialty pharmacies. Contact manufacturer or consult the cosibelimab-ipdl website ([Web]) for specific availability information.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 60 mg/mL | Unloxcyt™ | Checkpoint Therapeutics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions March 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Checkpoint Therapeutics, Inc. UNLOXCYT™ (cosibelimab-ipdl) injection prescribing information. Waltham, MA; 2024 December.
2. Clingan P, Ladwa R, Brungs D, et al. Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J Immunother Cancer. 2023;11(10):e007637.
3. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 761297Orig1s000: Multi-discipline review. 2024 Dec 13. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/761297Orig1s000MultidisciplineR.pdf
4. Ruiz E, Muñoz-Couselo E, Montaudié H, et al. Efficacy and safety of cosibelimab in advanced cutaneous squamous cell carcinoma: Results from a pivotal open-label study with a median follow-up of ≥2 years.
5. Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018;78(3):560-578.JADD
6. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014; 384:1109-17.
7. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PDo1-) in melanoma. N Engl J Med. 2013; 369:134-44.
8. Poole RM. Pembrolizumab: first global approval. Drugs. 2014; 74:1973-81.
9. Gentzler R, Hall R, Kunk PR, et al. Beyond melanoma: ihibiting the PD-1/PD-L1 pathway in solid tumors. Immunotherapy. 2016; 8:583-600.