Drug Detail:Yervoy (Ipilimumab [ ip-i-lim-ue-mab ])
Generic Name: IPILIMUMAB 5mg in 1mL
Dosage Form: injection
Drug Class: Anti-CTLA-4 monoclonal antibodies
Patient Selection
Select patients with metastatic NSCLC for treatment with YERVOY in combination with nivolumab based on PD-L1 expression [see Clinical Studies (14.6)].
Information on FDA-approved tests for the determination of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage
The recommended dosages of YERVOY as a single agent are presented in Table 1.
|
Indication |
Recommended YERVOY Dosage |
Duration of Therapy |
|
Unresectable or metastatic melanoma |
3 mg/kg every 3 weeks 30-minute intravenous infusion |
Maximum of 4 doses |
|
Adjuvant treatment of melanoma |
10 mg/kg every 3 weeks followed by 10 mg/kg every 12 weeks (90-minute intravenous infusion) |
Every 3 weeks up to a maximum of 4 doses Every 12 weeks for up to 3 years |
The recommended dosages of YERVOY in combination with other therapeutic agents are presented in Table 2. Refer to the respective Prescribing Information for each therapeutic agent administered in combination with YERVOY for recommended dosage information, as appropriate.
| * 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. ‡ 30-minute intravenous infusion on the same day. |
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|
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 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 |
1 mg/kg every 3 weeks‡ with nivolumab 3 mg/kg‡ |
After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.† |
|
Hepatocellular carcinoma |
3 mg/kg every 3 weeks‡ with nivolumab 1 mg/kg‡ |
In combination with nivolumab After completing 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 |
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|
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 (30-minute intravenous infusion) with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks (30-minute intravenous infusion) |
In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years |
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.
| 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 a Resume 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. b If 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. c This guidance is only applicable to HCC patients who are being treated with YERVOY in combination with nivolumab. d Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. |
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|
Adverse Reaction |
Severity* |
Dosage Modifications |
|
Immune-Mediated Adverse Reactions [See Warnings and Precautions (5.1)] |
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|
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 |
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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 |
|
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 solution 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.
