nivolumab (Rx)

Adjuvant Treatment of Melanoma

Indicated for melanoma in patients with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity for up to 1 year

Unresectable or Metastatic Melanoma

Indicated as a single agent or in combination with ipilimumab

Single agent

• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 1 mg/kg IV q3Weeks PLUS  
• Ipilimumab 3 mg/kg IV on the same day for maximum of 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer (NSCLC)

Monotherapy

• Indicated for metastatic NSCLC with progression in patients on or after platinum-based chemotherapy
• Patients with EGFR or ALK genomic tumor aberrations should have disease progression prior to initiation
• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination therapy with ipilimumab

• Indicated in combination with ipilimumab for first-line treatment of metastatic NSCLC in adults whose tumors express PD-L1 (≥1%) with no EGFR or ALK genomic tumor aberrations
• Nivolumab 3 mg/kg IV q2Weeks, PLUS  
• Ipilimumab 1 mg/kg IV q6Weeks
• Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Combination with ipilimumab and platinum chemotherapy

• Indicated in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment of metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic tumor aberrations
• Nivolumab 360 mg/kg IV q3Weeks, PLUS  
• Ipilimumab 1 mg/kg IV q6Weeks, PLUS
• Histology-based platinum doublet chemotherapy q3Weeks for 2 cycles
• Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Metastatic Small Cell Lung Cancer

Indicated for metastatic small cell lung cancer (SCLC) in patients with progression after platinum-based chemotherapy and at least 1 other line of therapy

240 mg IV q2Weeks

Continue until disease progression or unacceptable toxicity

Advanced Renal Cell Carcinoma

Single agent

• Indicated for advanced renal cell carcinoma in patients who have received prior antiangiogenic therapy
• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Indicated for patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma
• Nivolumab 3 mg/kg IV q3Weeks PLUS  
• Ipilimumab 1 mg/kg IV on the same day for 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity
• Also see ipilimumab drug monograph for dose

Hodgkin Lymphoma

Indicated for classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin, or ≥3 lines of systemic therapy (eg, autologous HSCT)

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Recurrent of Metastatic Squamous Head & Neck Carcinoma

Indicated for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in patients with disease progression on or after a platinum-based therapy

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Advanced or Metastatic Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Indicated as a single agent or in combination with ipilimumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

Single agent

• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 3 mg/kg IV q3Weeks PLUS  
• Ipilimumab 1 mg/kg IV on the same day for 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Hepatocellular Carcinoma

Indicated as a single agent or in combination with ipilimumab for hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib

Single agent

• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 1 mg/kg IV q3Weeks PLUS  
• Ipilimumab 3 mg/kg IV on the same day for 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Esophageal Squamous Cell Carcinoma

Indicated for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in patients previously treated with fluoropyrimidine- and platinum-based chemotherapy

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Malignant Pleural Mesothelioma

Indicated as first-line treatment for unresectable malignant pleural mesothelioma in combination with ipilimumab

Nivolumab 360 mg IV q3Weeks, PLUS

Ipilimumab 1 mg/kg IV q6Weeks

Continue in combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Dosage Modifications

Hypothyroidism or hyperthyroidism: No recommended dose modifications

Note: When administered in combination with ipilimumab, if nivolumab is withheld, ipilimumab should also be withheld

Renal impairment

• All severities: No dosage modifications required

Hepatic impairment

• Mild or moderate: No dosage modifications required
• Severe: Not studied

Infusion reactions

• Mild or moderate: Interrupt or slow infusion rate
• Severe or life-threatening: Discontinue

Withhold for any of the following

• Grade 2 pneumonitis
• Grade 2 diarrhea or colitis
• Grade 3 diarrhea or colitis (single-agent nivolumab)
• Grade 2 or 3 hypophysitis
• Grade 2 adrenal insufficiency
• Grade 3 hyperglycemia
• Encephalitis, new-onset moderate or severe neurologic signs or symptoms
• Grade 3 rash or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
• Serum creatinine >1.5-6 x ULN or >1.5x baseline
• Any other severe or grade 3 treatment-related adverse reaction
• May resume treatment for patients whose adverse reactions recover to grade 0-1

Permanently discontinue for any of the following

• Grade 3 or 4 pneumonitis
• Grade 3 diarrhea or colitis (nivolumab in combination with ipilimumab)
• Grade 4 diarrhea or colitis
• Grade 4 hypophysitis
• Grade 3 or 4 adrenal insufficiency
• Grade 4 hyperglycemia
• Grade 3 myocarditis
• Immune-mediated encephalitis
• Grade 4 rash or confirmed SJS or TEN
• Serum creatinine >6x ULN
• Recurrence of same grade 3 adverse reactions
• Life-threatening or Grade 4 adverse reaction Inability to reduce corticosteroid dose to ≤10 mg/day of prednisone or equivalent within 12 weeks
• Persistent grade 2 or 3 treatment-related adverse reactions within 12 weeks after the last dose

Hepatitis/non-HCC

• AST or ALT >3 to 5x ULN, or total bilirubin >1.5 to 3xULN: Withhold dose
• AST or ALT >5x ULN or total bilirubin >3x ULN: Permanently discontinue

Hepatitis/HCC

• AST or ALT within normal limits at baseline and increases to >3 to 5x ULN: Withhold dose
• AST or ALT >1 to 3x ULN at baseline and increases to >5 to 10x ULN: Withhold dose
• AST or ALT >3 to 5x ULN at baseline and increases to >8 to 10x ULN: Withhold dose
• AST or ALT increases to >10x ULN or total bilirubin increases to >3x ULN: Permanently discontinue

Dosing Considerations

Patient selection

• Combination therapy with ipilimumab for metastatic NSCLC should be based on PD-L1 expression
• Information on FDA-approved tests for the determination of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

Orphan Designations

Glioblastoma

Gastric cancer, including gastro-esophageal junction cancer

Anal cancer

Primary mediastinal B-cell lymphoma

Orphan sponsor

• Bristol-Myers Squibb Company; P. O. Box 4000; Princeton, New Jersey 08543

Microsatellite Instability-High Cancer

Indicated as a single agent or in combination with ipilimumab for patients aged ≥12 years with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

<12 years: Safety and efficacy not established

≥12 year

• Single agent

  • <40 kg: 3 mg/kg IV q2Weeks  
  • ≥40 kg: 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity

• Combination with ipilimumab

  • Nivolumab 3 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 1 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 3 mg/kg IV q2Weeks (patients <40 kg); 240 mg IV q2Weeks or 480 mg IV q4Weeks (patients ≥40 kg)
  • Continue until disease progression or unacceptable toxicity