Cosibelimab

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.

12.1. 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.

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. 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.

4. CONTRAINDICATIONS None. None.

5. WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions. Immune-mediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue UNLOXCYT based on the severity of reaction. Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue based on severity of reaction.

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Severe and fatal immune-mediated adverse reactions Infusion-related reactions Complications of Allogeneic HSCT 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. 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.

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.