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Yervoy

ipilimumab
CTLA-4 Inhibitor BMS FDA Approved 2011
Indications Dosing Forms Contraindications Warnings Adverse Reactions Pharmacology Clinical Studies Tumor Types
1. Indications and Usage

Unresectable or metastatic melanoma (monotherapy or with nivolumab); Adjuvant treatment of cutaneous melanoma with pathologic involvement of regional lymph nodes >1 mm who have undergone complete resection; Advanced renal cell carcinoma (with nivolumab, first-line intermediate/poor risk); Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (with nivolumab, after prior fluoropyrimidine/oxaliplatin/irinotecan); Hepatocellular carcinoma (with nivolumab, after prior sorafenib); Non-small cell lung cancer (with nivolumab, first-line metastatic); Malignant pleural mesothelioma (with nivolumab, first-line unresectable); Esophageal cancer (with nivolumab, first-line advanced/metastatic).

2. Dosage and Administration

Melanoma monotherapy: 3 mg/kg IV over 90 min q3w Γ— 4 doses
Melanoma adjuvant: 10 mg/kg IV q3w Γ— 4 doses, then q12w for up to 3 years
With nivolumab (RCC/CRC/HCC/NSCLC/meso/esophageal): 1 mg/kg IV q3w for 4 doses (with nivo 3 mg/kg), then nivo maintenance
With nivolumab (melanoma): 3 mg/kg IV q3w Γ— 4 doses (with nivo 1 mg/kg)

3. Dosage Forms and Strengths

Injection: 5 mg/mL in 10 mL (50 mg) and 40 mL (200 mg) single-dose vials

4. Contraindications

None listed.

5. Warnings and Precautions
⚠ Boxed Warning
None (but extensive immune-mediated warnings)
  • Immune-Mediated Colitis: In 12% monotherapy (Grade 3-4: 7%). Fatal intestinal perforation reported. D/C for Grade 3-4.
  • Immune-Mediated Hepatitis: Grade 3-5 in 2-7% (with nivolumab up to 15%). Fatal hepatotoxicity reported. Monitor LFTs before each dose.
  • Immune-Mediated Dermatitis: Severe including TEN and DRESS. Rash in 24%.
  • Immune-Mediated Neuropathies: Including fatal Guillain-BarrΓ© and myasthenia gravis.
  • Immune-Mediated Endocrinopathies: Hypophysitis (13% at 10 mg/kg), hypothyroidism (4%), hyperthyroidism, adrenal insufficiency.
  • Other Immune-Mediated: Nephritis, pneumonitis, uveitis, pancreatitis, myocarditis.
6. Adverse Reactions
Most Common Adverse Reactions

Fatigue (42%), diarrhea (33%), pruritus (31%), rash (29%), colitis (12%), nausea (26%), decreased appetite (17%), vomiting (15%), headache (14%), abdominal pain (12%), weight decrease (12%)

Fatigue
42%
Diarrhea
33%
Pruritus
31%
Rash
29%
Nausea
26%
Decreased Appetite
17%
Vomiting
15%
Headache
14%
Colitis
12%
Abdominal Pain
12%

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

12. Clinical Pharmacology
Mechanism of Action

Ipilimumab is a human IgG1ΞΊ monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is an immune checkpoint receptor that functions as an immune attenuator, competing with CD28 for binding to B7 ligands on antigen-presenting cells. By blocking CTLA-4, ipilimumab augments T-cell activation and proliferation, including tumor-infiltrating T-effector cells, and reduces T-regulatory cell function, leading to enhanced anti-tumor immune responses.

Pharmacokinetics

Half-life: 14.7 days. Clearance: 15.3 mL/h. Vd: 7.2 L. Steady-state reached by the 3rd dose with q3w dosing. Linear PK from 0.3-10 mg/kg. Not affected by body weight, age, gender, or hepatic/renal function.

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
πŸ“‹ All Ipilimumab Trials on ClinicalTrials.gov β†— πŸ“š PubMed: Ipilimumab Clinical Trials β†—