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 PDL1 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.

Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma and advanced RCC. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity.

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.

 See Full Prescribing Information for other indications.

• 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. 
  • Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.

See Full Prescribing Information for dosage and administration for other indications.

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.

• In combination with platinum-doublet chemotherapy: nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.

• In combination with ipilimumab and platinum-doublet chemotherapy: fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

• In combination with cabozantinib: diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

• In combination with fluoropyrimidine- and platinum-containing chemotherapy: nausea, peripheral neuropathy, decreased appetite, fatigue, constipation, stomatitis, diarrhea, vomiting, abdominal pain, and musculoskeletal pain.

• 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.
• Complications of allogeneic HSCT: Fatal and other serious complications can occur in patient who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.
• Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.
• Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.