HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------DOSAGE AND ADMINISTRATION-------------------­ These highlights do not include all the information needed to use OPDIVO • Administer by intravenous infusion based upon recommended infusion rate safely and effectively. See full prescribing information for OPDIVO. for each indication. (2) OPDIVO (nivolumab) injection, for intravenous use • Unresectable or metastatic melanoma Initial U.S. Approval: 2014 • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks --------------------------RECENT MAJOR CHANGES---------------------------­ for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) Indications and Usage (1) 1/2021 • Adjuvant treatment of melanoma Dosage and Administration (2) 1/2021 • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) Warnings and Precautions (5) 1/2021 • Metastatic non-small cell lung cancer ---------------------------INDICATIONS AND USAGE---------------------------­ • 3 mg/kg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks. (2.2) OPDIVO is a programmed death receptor-1 (PD-1) blocking antibody indicated • 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and for the treatment of: 2 cycles of platinum-doublet chemotherapy. (2.2) Melanoma • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • patients with unresectable or metastatic melanoma, as a single agent or in • Malignant pleural mesothelioma combination with ipilimumab. (1.1) • 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks. (2.2) • patients with melanoma with lymph node involvement or metastatic disease • Advanced renal cell carcinoma who have undergone complete resection, in the adjuvant setting. (1.2) • 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks Non-Small Cell Lung Cancer (NSCLC) for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • adult patients with metastatic non-small cell lung cancer expressing PD-L1 • 240 mg every 2 weeks or 480 mg every 4 weeks administered in (≥1%) as determined by an FDA-approved test, with no EGFR or ALK combination with cabozantinib 40 mg once daily without food. (2.2) genomic tumor aberrations, as first-line treatment in combination with • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) ipilimumab. (1.3) • Classical Hodgkin lymphoma • adult patients with metastatic or recurrent non-small cell lung cancer with no • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) EGFR or ALK genomic tumor aberrations as first-line treatment, in • Recurrent or metastatic squamous cell carcinoma of the head and neck combination with ipilimumab and 2 cycles of platinum-doublet • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) chemotherapy. (1.3) • Locally advanced or metastatic urothelial carcinoma • patients with metastatic non-small cell lung cancer and progression on or • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) after platinum-based chemotherapy. Patients with EGFR or ALK genomic • Microsatellite instability-high (MSI-H) or mismatch repair deficient tumor aberrations should have disease progression on FDA-approved (dMMR) metastatic colorectal cancer therapy for these aberrations prior to receiving OPDIVO. (1.3) • Adult and pediatric patients ≥ 40 kg: 240 mg every 2 weeks or 480 mg Malignant Pleural Mesothelioma every 4 weeks. (2.2) • adult patients with unresectable malignant pleural mesothelioma, as first-line • Pediatric patients < 40 kg: 3 mg/kg every 2 weeks. (2.2) treatment in combination with ipilimumab. (1.4) • Adult and pediatric patients ≥ 40 kg: 3 mg/kg followed by ipilimumab Renal Cell Carcinoma (RCC) 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 • patients with intermediate or poor risk advanced renal cell carcinoma, as a weeks or 480 mg every 4 weeks. (2.2) first-line treatment in combination with ipilimumab. (1.5) • Hepatocellular carcinoma • patients with advanced renal cell carcinoma, as a first-line treatment in • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) combination with cabozantinib. (1.5) • 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks • patients with advanced renal cell carcinoma who have received prior anti­ for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) angiogenic therapy. (1.5) • Classical Hodgkin Lymphoma (cHL) Esophageal squamous cell carcinoma • 240 mg every 2 weeks or 480 mg every 4 weeks. (2.2) • adult patients with classical Hodgkin lymphoma that has relapsed or a progressed after : (1.6) ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ • autologous hematopoietic stem cell transplantation (HSCT) and • Injection: 40 mg/4 mL, 100 mg/10 mL, and 240 mg/24 mL solution in a brentuximab vedotin, or single-dose vial. (3) • 3 or more lines of systemic therapy that includes autologous HSCT. Squamous Cell Carcinoma of the Head and Neck (SCCHN) ------------------------------CONTRAINDICATIONS------------------------------­ • patients with recurrent or metastatic squamous cell carcinoma of the head • None. (4) and neck with disease progression on or after a platinum-based therapy. (1.7) -----------------------WARNINGS AND PRECAUTIONS-----------------------­ Urothelial Carcinoma • Immune-Mediated Adverse Reactions: (5.1) • patients with locally advanced or metastatic urothelial carcinoma whoa: o Immune-mediated adverse reactions, which may be severe or fatal, can • have disease progression during or following platinum-containing occur in any organ system or tissue, including the following: immune- chemotherapy mediated pneumonitis, immune-mediated colitis, immune-mediated • have disease progression within 12 months of neoadjuvant or adjuvant hepatitis and hepatotoxicity, immune-mediated endocrinopathies, treatment with platinum-containing chemotherapy. (1.8) immune-mediated dermatologic adverse reactions, and immune- Colorectal Cancer mediated nephritis and renal dysfunction. • adult and pediatric (12 years and older) patients with microsatellite o Monitor for early identification and management. Evaluate liver enzymes, instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic creatinine, and thyroid function at baseline and periodically during colorectal cancer that has progressed following treatment with a treatment. fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in Withhold or permanently discontinue based on severity and type of a o combination with ipilimumab. (1.9) reaction. (2.3) Hepatocellular Carcinoma (HCC) • Infusion-related reactions: Interrupt, slow the rate of infusion, or • patients with hepatocellular carcinoma who have been previously treated permanently discontinue OPDIVO based on severity of reaction. (5.2) a with sorafenib, as a single agent or in combination with ipilimumab. (1.10) • Complications of allogeneic HSCT: Fatal and other serious complications Esophageal Squamous Cell Carcinoma (ESCC) can occur in patient who receive allogeneic HSCT before or after being • patients with unresectable advanced, recurrent or metastatic esophageal treated with a PD-1/PD-L1 blocking antibody. (5.3) squamous cell carcinoma after prior fluoropyrimidine- and platinum-based • Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive chemotherapy. (1.11) potential of potential risk to a fetus and to use effective contraception. (5.4, a This indication is approved under accelerated approval based on overall 8.1, 8.3) response rate and duration of response. Continued approval for this • Treatment of patients with multiple myeloma with a PD-1 or PD-L1 indication may be contingent upon verification and description of clinical blocking antibody in combination with a thalidomide analogue plus benefit in confirmatory trials. 1 Reference ID: 4734770 dexamethasone is not recommended outside of controlled clinical trials. • In combination with cabozantinib: diarrhea, fatigue, hepatotoxicity, palmar­ (5.5) plantar erythrodysaesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, ------------------------------ADVERSE REACTIONS-----------------------------­ dysgeusia, abdominal pain, cough, and upper respiratory tract infection. (6.1) Most common adverse reactions (incidence ≥20%) in patients were: • As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or pain, arthralgia, upper respiratory tract infection, pyrexia, headache, www.fda.gov/medwatch. abdominal pain, and vomiting. (6.1) -----------------------USE IN SPECIFIC POPULATIONS----------------------­ • In combination with ipilimumab: fatigue, diarrhea, rash, pruritus, nausea, • Lactation: Advise not to breastfeed. (8.2) musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, See 17 for PATIENT COUNSELING INFORMATION and Medication headache, hypothyroidism, decreased weight, and dizziness. (6.1) Guide. • In combination with ipilimumab and platinum-doublet chemotherapy: fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus. (6.1) Revised: 1/2021 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS 1.1 Unresectable or Metastatic Melanoma 8.1 Pregnancy