Yervoy (Ipilimumab)

YERVOY is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for:

• •Treatment of unresectable or metastatic melanoma in adults and pediatric patients 12 years and older as a single agent or in combination with nivolumab.
  1.1 Unresectable or Metastatic Melanoma

  YERVOY, as a single agent or in combination with nivolumab, is indicated for the treatment of unresectable or metastatic melanoma in adult and pediatric patients 12 years and older.
• •Adjuvant treatment of adult patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
  1.2 Adjuvant Treatment of Melanoma

  YERVOY is indicated for the adjuvant treatment of adult patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

• •Treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma, as first-line treatment in combination with nivolumab.
  1.3 Advanced Renal Cell Carcinoma

  YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

• •Treatment of adults and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) in combination with nivolumab.
  1.4 Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

  • •YERVOY, in combination with nivolumab, is indicated for the treatment of adult and pediatric patients 12 years and older with
    unresectable or metastatic
    microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (
    CRC
    ).

• •adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) as first-line treatment in combination with nivolumab. (
  1.5 Hepatocellular Carcinoma

  • •YERVOY, in combination with nivolumab, is indicated for the
    first-line
    treatment of adult patients with
    unresectable or metastatic
    hepatocellular carcinoma (HCC).
  • •
    YERVOY, in combination with nivolumab, is indicated for the treatment of adult patients with unresectable or metastatic HCC
    who have been previously treated with sorafenib.
  )
• •in combination with nivolumab in adult patients with unresectable or metastatic HCC who have been previously treated with sorafenib.
  1.5 Hepatocellular Carcinoma

  • •YERVOY, in combination with nivolumab, is indicated for the
    first-line
    treatment of adult patients with
    unresectable or metastatic
    hepatocellular carcinoma (HCC).
  • •
    YERVOY, in combination with nivolumab, is indicated for the treatment of adult patients with unresectable or metastatic HCC
    who have been previously treated with sorafenib.

• •Treatment of adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab.
  1.6 Metastatic Non-Small Cell Lung Cancer

  YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test

  [see Dosage and Administration (2.1)]

  , with no EGFR or ALK genomic tumor aberrations.

  YERVOY, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations.
• •Treatment of adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy.
  1.6 Metastatic Non-Small Cell Lung Cancer

  YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test

  [see Dosage and Administration (2.1)]

  , with no EGFR or ALK genomic tumor aberrations.

  YERVOY, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations.

• •Treatment of adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with nivolumab.
  1.7 Malignant Pleural Mesothelioma

  YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

• •Treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, as first line treatment in combination with nivolumab whose tumors express PD-L1 (≥1).
  1.8 Esophageal Cancer

  YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC)

  whose tumors express PD-L1 (≥1)

  [see Dosage and Administration (2.1)]

  .

• •Administer by intravenous infusion after dilution based upon recommended infusion rate for each indication.
  2 DOSAGE AND ADMINISTRATION

  • •Administer by intravenous infusion after dilution based upon recommended infusion rate for each indication. (2)
  • •
    Unresectable or Metastatic Melanoma
    :
    • ∘YERVOY 3 mg/kg every 3 weeks for a maximum of 4 doses. (2.2)
    • ∘YERVOY 3 mg/kg immediately following nivolumab 1 mg/kg on the same day, every 3 weeks for 4 doses. After completing 4 doses of the combination, administer nivolumab as a single agent as recommended in the Full Prescribing Information for nivolumab. (2.2)
  • •
    Adjuvant Treatment of Melanoma
    : YERVOY 3 mg/kg every 3 weeks for 4 doses, followed by 3 mg/kg every 12 weeks for up to 4 additional doses. (2.2)
  • •
    Advanced Renal Cell Carcinoma
    : YERVOY 1 mg/kg immediately following nivolumab 3 mg/kg on the same day, every 3 weeks for 4 doses. After completing 4 doses of the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab. (2.2)
  • •
    Treatment of microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in combination with nivolumab
    :
    • ∘Adult and pediatric patients weighing 40 kg or greater: YERVOY 1 mg/kg immediately following nivolumab 240 mg on the same day every 3 weeks for a maximum of 4 doses. After completing the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab. (2.2)
    • ∘Pediatric patients weighing less than 40 kg: YERVOY 1 mg/kg immediately following nivolumab 3 mg/kg on the same day every 3 weeks for a maximum of 4 doses. After completing the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab.
  • •
    Hepatocellular Carcinoma
    : YERVOY 3 mg/kg intravenously over 30 minutes immediately following nivolumab 1 mg/kg intravenously over 30 minutes on the same day, every 3 weeks for up to 4 doses. After completing up to 4 doses of the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab. (2.2)
  • •
    Metastatic non-small cell lung cancer
    :
    • ∘YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks. (2.2)
    • ∘YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and 2 cycles of platinum-doublet chemotherapy. (2.2)
  • •
    Malignant pleural mesothelioma
    : YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks. (2.2)
  • •
    Esophageal squamous cell carcinoma:
    YERVOY 1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks. (2.2)
  • •See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions.

  2.1 Patient Selection

  Information on FDA-approved tests for patient selection is available at:

  https://www.fda.gov/CompanionDiagnostics

  Non-Small Cell Lung Cancer

  • •Select patients with metastatic NSCLC for treatment with YERVOY in combination with nivolumab based on PD-L1 expression
    [see Clinical Studies (14.6)]
    .

  Esophageal Cancer

  • •
    Select patients with unresectable or advanced or metastatic ESCC for treatment with YERVOY in combination with nivolumab based on PD-L1 expression
    [see Clinical Studies (14.8)]
    .
  • •
    An FDA-approved companion diagnostic for the detection of PD-L1 expression in patients with advanced or metastatic ESCC is not available.

  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.

  2.3 Recommended Dosage Modifications for Adverse Reactions

  No dose reduction for YERVOY is recommended. In general, withhold YERVOY for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue YERVOY for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, persistent moderate (Grade 2) or severe (Grade 3) reactions lasting 12 weeks or longer after last YERVOY dose (excluding endocrinopathy), or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids. Dosage modifications for YERVOY or YERVOY in combination with nivolumab for adverse reactions that require management different from these general guidelines are summarized in Table 3.

  When YERVOY is administered in combination with nivolumab, withhold or permanently discontinue both YERVOY and nivolumab for toxicity.

  Table 3: Recommended Dosage Modifications for Adverse Reactions

  ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit of normal *Based on Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 aResume in patients with complete or partial resolution (Grade 0 or 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids. bIf AST/ALT are less than or equal to ULN at baseline, withhold or permanently discontinue YERVOY based on recommendations for hepatitis with no liver involvement. cThis guidance is only applicable to HCC patients who are being treated with YERVOY in combination with nivolumab. dDepending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.
  Adverse Reaction	Severity*	Dosage Modifications
  Immune-Mediated Adverse Reactions [See Warnings and Precautions (5.1)]
  Colitis	Grade 2	Withholda
  	Grade 3 or 4	Permanently discontinue
  Hepatitis with no tumor involvement of the liver or Hepatitis with tumor involvement of the liver/non-HCC	AST or ALT increases to more than 3 times and up to 5 times the ULN or Total bilirubin increases to more than 1.5 times and up to 3 times the ULN	Withholda
  	AST or ALT more than 5 times the ULN or Total bilirubin more than 3 times the ULN	Permanently discontinue
  Hepatitis with tumor involvement of the liverb/HCCc	Baseline AST/ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST/ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN.	Withholda
  	AST/ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN.	Permanently discontinue
  Exfoliative Dermatologic Conditions	Suspected SJS, TEN, or DRESS	Withhold
  	Confirmed SJS, TEN, or DRESS	Permanently discontinue
  Endocrinopathiesd	Grades 3 or 4	Withhold until clinically stable or permanently discontinue depending on severity
  Pneumonitis	Grade 2	Withholda
  	Grade 3 or 4	Permanently discontinue
  Nephritis with Renal Dysfunction	Grade 2 or 3 increased blood creatinine	Withholda
  	Grade 4 increased blood creatinine	Permanently discontinue
  Neurological Toxicities	Grade 2	Withholda
  	Grade 3 or 4	Permanently discontinue
  Myocarditis	Grade 2, 3 or 4	Permanently discontinue
  Ophthalmologic	Grade 2, 3, or 4 that does not improve to Grade 1 within 2 weeks while receiving topical therapy or that requires systemic treatment	Permanently discontinue
  Other Adverse Reactions
  Infusion-Related Reactions [see Warnings and Precautions (5.2)]	Grade 1 or 2	Interrupt or slow the rate of infusion
  	Grade 3 or 4	Permanently discontinue

  2.4 Preparation and Administration

  • •Do not shake product.
  • •Visually inspect for particulate matter and discoloration prior to administration. Discard vial if solution is cloudy, there is pronounced discoloration (solution may have pale-yellow color), or there is foreign particulate matter other than translucent-to-white, amorphous particles.

  Preparation of Solution

  • •Allow the vial(s) to stand at room temperature for approximately 5 minutes prior to preparation of infusion.
  • •Withdraw the required volume of YERVOY and transfer into an intravenous bag.
  • •Dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a
    final concentration ranging from 1 mg/mL to 2 mg/mL

    .
    Mix diluted solution by gentle inversion.
  • •After preparation, store the diluted solution either refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature of 20°C to 25°C (68°F to 77°F) for no more than 24 hours from the time of preparation to the time of infusion.
  • •Discard partially used or empty vials of YERVOY.

  Administration

  • •Do not co-administer other drugs through the same intravenous line.
  • •Flush the intravenous line with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after each dose.
  • •Administer diluted YERVOY solution by intravenous infusion over 30 minutes through an intravenous line containing a sterile, non-pyrogenic,
    low-protein
    -binding in-line filter.
  • •When administered in combination with nivolumab, infuse nivolumab first followed by YERVOY on the same day.
  • •When administered with nivolumab and platinum-doublet chemotherapy, infuse nivolumab first followed by YERVOY and then platinum-doublet chemotherapy on the same day.
  • •Use separate infusion bags and filters for each infusion.
• •
  Unresectable or Metastatic Melanoma
  :
  • ∘YERVOY 3 mg/kg every 3 weeks for a maximum of 4 doses.
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
  • ∘YERVOY 3 mg/kg immediately following nivolumab 1 mg/kg on the same day, every 3 weeks for 4 doses. After completing 4 doses of the combination, administer nivolumab as a single agent as recommended in the Full Prescribing Information for nivolumab.
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Adjuvant Treatment of Melanoma
  : YERVOY 3 mg/kg every 3 weeks for 4 doses, followed by 3 mg/kg every 12 weeks for up to 4 additional doses.
  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Advanced Renal Cell Carcinoma
  : YERVOY 1 mg/kg immediately following nivolumab 3 mg/kg on the same day, every 3 weeks for 4 doses. After completing 4 doses of the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab.
  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Treatment of microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in combination with nivolumab
  :
  • ∘Adult and pediatric patients weighing 40 kg or greater: YERVOY 1 mg/kg immediately following nivolumab 240 mg on the same day every 3 weeks for a maximum of 4 doses. After completing the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab.
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
  • ∘Pediatric patients weighing less than 40 kg: YERVOY 1 mg/kg immediately following nivolumab 3 mg/kg on the same day every 3 weeks for a maximum of 4 doses. After completing the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab. (
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
    )
• •
  Hepatocellular Carcinoma
  : YERVOY 3 mg/kg intravenously over 30 minutes immediately following nivolumab 1 mg/kg intravenously over 30 minutes on the same day, every 3 weeks for up to 4 doses. After completing up to 4 doses of the combination, administer nivolumab as a single agent as recommended in Full Prescribing Information for nivolumab.
  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Metastatic non-small cell lung cancer
  :
  • ∘YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks.
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
  • ∘YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and 2 cycles of platinum-doublet chemotherapy.
    2.2 Recommended Dosage

    The recommended dosages of YERVOY as a single agent are presented in Table 1.

    Administer YERVOY as a 30-minute intravenous infusion

    [see Preparation and Administration (2.4)]

    .

    Table 1: Recommended Dosages for YERVOY as a Single Agent

    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
    Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

    The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

    Administer YERVOY on the same day as other therapeutic agents.

    Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

    Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

    *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
    Indication	Recommended YERVOY Dosage	Duration of Therapy
    Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
    Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
    	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
    Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
    Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    		2 cycles of histology-based platinum-doublet chemotherapy
    Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
    Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Malignant pleural mesothelioma
  : YERVOY 1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks.
  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •
  Esophageal squamous cell carcinoma:
  YERVOY 1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks.
  2.2 Recommended Dosage

  The recommended dosages of YERVOY as a single agent are presented in Table 1.

  Administer YERVOY as a 30-minute intravenous infusion

  [see Preparation and Administration (2.4)]

  .

  Table 1: Recommended Dosages for YERVOY as a Single Agent

  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks	Maximum of 4 doses
  Adjuvant treatment of melanoma	3 mg/kg every 3 weeks followed by 3 mg/kg every 12 weeks	Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 4 additional doses

  The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2.

  Administer YERVOY on the same day as other therapeutic agents.

  Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.

  Table 2: Recommended Dosages of YERVOY in Combination with Other Therapeutic Agents*

  *Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. †Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY.
  Indication	Recommended YERVOY Dosage	Duration of Therapy
  Unresectable or metastatic melanoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.†
  Advanced renal cell carcinoma	1 mg/kg every 3 weeks with nivolumab 3 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer	Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more: 1 mg/kg every 3 weeks with nivolumab 240 mg	In combination with nivolumab for a maximum of 4 doses .† After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity , or up to 2 years .†
  	Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg
  Hepatocellular carcinoma	3 mg/kg every 3 weeks with nivolumab 1 mg/kg	In combination with nivolumab for a maximum of 4 doses. After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.†
  Metastatic non-small cell lung cancer expressing PD‑L1	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Metastatic or recurrent non-small cell lung cancer	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks and histology-based platinum‑doublet chemotherapy every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  		2 cycles of histology-based platinum-doublet chemotherapy
  Malignant pleural mesothelioma	1 mg/kg every 6 weeks with nivolumab 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.†
  Esophageal squamous cell carcinoma	1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks	In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years.
• •See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions.

Injection: 50 mg/10 mL (5 mg/mL) and 200 mg/40 mL (5 mg/mL) as a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose vial.

• •
  Lactation
  : Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There are no data on the presence of YERVOY in human milk or its effects on the breastfed child or milk production. In monkeys, ipilimumab was present in milk

  (see Data)

  . Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with YERVOY and for 3 months following the last dose.

  Data

  In monkeys treated at dose levels resulting in exposures 2.6 and 7.2 times higher than those in humans at a 3 mg/kg dose, ipilimumab was present in milk at concentrations of 0.1 mcg/mL and 0.4 mcg/mL, representing a ratio of up to 0.3% of the steady-state serum concentration of the drug.
  )