Avelumab

BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for: Merkel Cell Carcinoma (MCC) Adults and pediatric patients 12 years and older with metastatic MCC. Urothelial Carcinoma (UC) Maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy. Patients with locally advanced or metastatic UC who: Have disease progression during or following platinum-containing chemotherapy. Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Renal Cell Carcinoma (RCC) First-line treatment, in combination with axitinib, of patients with advanced RCC.

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. Avelumab 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 immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

Premedicate for the first 4 infusions and subsequently as needed. Merkel Cell Carcinoma: 800 mg every 2 weeks. Urothelial Carcinoma, 800 mg every 2 weeks. Renal Cell Carcinoma: 800 mg every 2 weeks in combination with axitinib 5 mg orally twice daily. Administer BAVENCIO as an intravenous infusion over 60 minutes.

None. None.

Immune-Mediated Adverse Reactions. Immune-mediated adverse reactions, which may be severe or fatal, 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 nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and may result in 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 based on severity and type of reaction. Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue BAVENCIO based on severity of reaction.

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 Major adverse cardiovascular events Most common adverse reactions (≥ 20%) in patients were: MCC: Fatigue, musculoskeletal pain, infusion-related reaction, rash, nausea, constipation, cough, and diarrhea. UC: Maintenance treatment: fatigue, musculoskeletal pain, urinary tract infection, and rash. Previously-treated: fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection. RCC (with axitinib): diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache.

Store refrigerated at 36°F to 46°F (2°C to 8°C) in original package to protect from light. Do not freeze or shake the vial.