Nivolumab

OPDIVO is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of: Melanoma • adult and pediatric (12 years and older) patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab. • for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. Non-Small Cell Lung Cancer (NSCLC) • adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer in the neoadjuvant setting, in combination with platinum-doublet chemotherapy.

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

• Administer by intravenous infusion after dilution based upon recommended infusion rate for each indication. • Unresectable or metastatic melanoma • Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks. • Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. • Adult and pediatric patients weighing 40 kg or greater: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. • Pediatric patients weighing less than 40 kg: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. • Adjuvant treatment of melanoma • Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks.

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 and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction. • 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 OPDIVO 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 Most common adverse reactions (incidence ≥20%) in patients were: • As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection. • In combination with ipilimumab: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness.

Store under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light by storing in the original package until time of use.