Cosibelimab

FDA Drug Information • Also known as: Unloxcyt

Brand Names: Unloxcyt
Dosage Form: LIQUID
Product Type: BULK INGREDIENT

Description

11. DESCRIPTION Cosibelimab-ipdl is a human programmed death ligand-1 (PD-L1) blocking antibody. Cosibelimab-ipdl is a human IgG1 lambda monoclonal antibody. Cosibelimab-ipdl is produced in Chinese hamster ovary (CHO) cells and has a calculated molecular weight of approximately 147 kDa. UNLOXCYT (cosibelimab-ipdl) injection for intravenous use is a sterile, preservative-free, clear to opalescent, colorless to yellow or slightly brown solution. It is supplied in single-dose vials. Each vial contains 300 mg of UNLOXCYT in 5 mL of solution with a pH of 5.3. Each mL of solution contains 60 mg of cosibelimab-ipdl, acetic acid (0.24 mg), mannitol (37.35 mg), polysorbate 80 (1.1 mg), sodium acetate (1.31 mg), sodium chloride (4.09 mg), and Water for Injection, USP.

What Is Cosibelimab Used For?

1. INDICATIONS AND USAGE UNLOXCYT 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. UNLOXCYT is a programmed death ligand-1 (PD-L1) blocking antibody 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.

Dosage and Administration

2. DOSAGE AND ADMINISTRATION The recommended dosage of UNLOXCYT is 1,200 mg as an intravenous infusion over 60 minutes every 3 weeks. ( 2.1 ) 2.1. Recommended Dosage The recommended dosage of UNLOXCYT is 1,200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity. 2.2. Dose Modifications for Adverse Reactions No dose reductions of UNLOXCYT are recommended. In general, withhold UNLOXCYT for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue UNLOXCYT for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to a prednisone equivalent of 10 mg or less per day within 12 weeks of initiating steroids. Dosage modifications for UNLOXCYT for adverse reactions that require management different from these general guidelines are summarized in Table 1. Table 1: Recommended Dose Modifications for Adverse Reactions Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 5. UNLOXCYT Dosage Modifications ALT = alanine aminotransferase; AST = aspartate aminotransferase; DRESS: drug rash with eosinophilia and systemic symptoms; SJS: Stevens-Johnson Syndrome; TEN: toxic epidermal necrolysis; ULN: upper limit of normal. Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce corticosteroid to a prednisone equivalent of 10 mg/day or less within 12 weeks of initiating steroids. Grade 3 or 4 Permanently discontinue Colitis Grade 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue UNLOXCYT based on recommendations for hepatitis with no tumor involvement of the liver. Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom...

Side Effects (Adverse Reactions)

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1) ] Infusion-related reactions [see Warnings and Precautions (5.2) ] Complications of Allogeneic HSCT [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800- 818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to UNLOXCYT as a single agent in 223 patients in two open-label, single-arm, multicohort studies, including 141 patients with advanced CSCC and 82 patients with other solid tumors and hematologic malignancies. UNLOXCYT was administered intravenously at doses of 800 mg every 2 weeks (n=174), 1,200 mg every 3 weeks (n=35), or other doses (n=14). Among the 223 patients, 54% were exposed for ≥24 weeks and 17% were exposed for ≥72 weeks. The safety of UNLOXCYT was evaluated in Study CK-301-101 in 141 patients with metastatic or locally advanced disease CSCC [see Clinical Studies (14) ] . Patients received UNLOXCYT 800 mg every 2 weeks (n=115) or 1,200 mg every 3 weeks (n=26) as an intravenous infusion until disease progression or unacceptable toxicity. The median duration of exposure was 36 weeks (2 weeks to 3.7 years). Serious adverse reactions occurred in 31% of advanced patients with CSCC who received UNLOXCYT. The most frequent serious adverse reactions (≥ 2% of patients) were sepsis (2.8%), pneumonia (2.8%) and pyrexia (2.1%). Permanent discontinuation of UNLOXCYT due to an adverse reaction occurred in 8% of patients. Adverse reactions resulting in permanent discontinuation of UNLOXCYT were COVID-19, COVID-19 pneumonia, sepsis, ulcerative keratitis, tumor thrombosis, axillary pain, paresthesia, cholestasis, hepatic cytolysis, wound hemorrhage, neck pain, pemphigoid, and eye pain (1 patient each). Dosage interruptions due to an adverse reaction occurred in 36% of patients who received UNLOXCYT. The adverse reaction that required dosage interruption in ≥ 2% of patients who received UNLOXCYT was COVID-19 (2%). The most common (≥ 10%) adverse reactions were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection. Table 2 and Table 3 summarize adverse reactions and laboratory abnormalities, respectively in CK-301-101. Table 2: Adverse Reactions in ≥ 10% of Patients with Metastatic or Locally Advanced CSCC Receiving UNLOXCYT in Study CK-301-101 UNLOXCYT N = 141 % System Organ Class Preferred Term All Grades % Grade 3 or 4 % Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03 (or later version) General disorders and administrative site conditions Fatigue Represents a composite of multiple related terms 33 3 Edema 11 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain 25 3 Skin and subcutaneous tissue disorders Rash 23 1 Pruritus 12 0 Endocrine disorder Hypothyroidism 14 0 Gastrointestinal disorders Diarrhea 14 0 Nausea 13 0 Constipation 13 0 Nervous system disorders Headache 12 0 Infections and infestations Localized infection 10 0.7 Urinary tract infection 10 0 Table 3: Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥ 1% of Patients with...

Contraindications

4. CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1. Pregnancy Risk Summary Based on its mechanism of action, UNLOXCYT can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of UNLOXCYT 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 (see Data ) . 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. Data Animal Data : Animal reproduction studies have not been conducted with cosibelimab-ipdl to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering UNLOXCYT during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to UNLOXCYT may increase the risk of developing immune-mediated disorders or altering the normal immune response.

How Supplied

16. HOW SUPPLIED/STORAGE AND HANDLING UNLOXCYT (cosibelimab-ipdl) injection is a clear to opalescent, colorless to yellow or slightly brown solution supplied in a carton containing one 300 mg/5 mL (60 mg/mL), single-dose vial (NDC 70095-130-01). Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.