Ipilimumab (Yervoy)

General information

Class/mechanism: Anti-CTLA-4 antibody. CTLA-4 is a negative regulator of T-cell activation and ipilimumab interferes with the ability of CTLA-4 to interact with its ligands CD80/CD86. CTLA-4 blockade results in T-cell activation and proliferation, and it is suspected that its anti-neoplastic activity may be due to T-cell mediated anti-tumor immune responses.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Toxicity management

• YERVOY Risk Evaluation and Mitigation Strategy (REMS) Site
• Immunotherapy toxicity management

Diseases for which it is established (work in progress)

• Hepatocellular carcinoma
• Melanoma
  • Uveal melanoma
• Malignant pleural mesothelioma
• Non-small cell lung cancer
  • Non-small cell lung cancer, nonsquamous
  • Non-small cell lung cancer, squamous
• Renal cell carcinoma

Diseases for which it is used

• CNS melanoma
• Colorectal cancer
• Esophageal squamous cell carcinoma
• Prostate cancer
• Small cell lung cancer

Patient drug information

• Ipilimumab (Yervoy) package insert
• Ipilimumab (Yervoy) patient drug information (Chemocare)
• Ipilimumab (Yervoy) patient drug information (UpToDate)

History of changes in FDA indication

Colorectal cancer

• 2018-07-10: Accelerated approval for treatment of adult and pediatric patients 12 years of age and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in combination with nivolumab. (New disease entity; based on CheckMate 142)

Hepatocellular carcinoma

• 2020-03-10: Accelerated approval in combination with nivolumab for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (Based on CheckMate 040)

Melanoma

• 2011-03-25: FDA approved for the treatment of unresectable or metastatic melanoma. (Initial approval; based on MDX010-20)
• 2015-10-28: FDA approved for adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy. (Approval extended to adjuvant setting; based on EORTC 18071)

Malignant pleural mesothelioma

• 2020-10-02: Approved in combination with nivolumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma. (New disease entity; based on CheckMate 743)

Non-small cell lung cancer

• 2020-05-15: Approved in combination with nivolumab as first-line treatment for patients with metastatic non-small cell lung cancer whose tumors express PD-L1 (≥1%), as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. (New disease entity; based on CheckMate 227)
• 2020-05-26: Approved in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. (PD-L1 expression requirement removed when given with chemotherapy; based on CheckMate 9LA)

Renal cell carcinoma

• 2018-04-16: FDA approved to be used in combination with Nivolumab (Opdivo) for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma. (New disease entity; based on CheckMate 214)

History of changes in EMA indication

• 2011-07-13: Initial marketing authorization as Yervoy.

History of changes in Health Canada indication

• 2012-02-01: Initial notice of compliance for the treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease.
• 2014-09-10: Revised indication for the treatment of unresectable or metastatic melanoma.
• 2017-04-13: New indication in combination with Opdivo (nivolumab) for the treatment of unresectable or metastatic melanoma in previously untreated adults.
• 2018-12-04: New indication in combination with Opdivo (nivolumab) for the treatment of adult patients with intermediate/poor-risk advanced or metastatic renal cell carcinoma.
• 2022-03-03: New reduction of indication for Unresectable or Metastatic Melanoma (unclear details).
• 2022-03-03: New indications in combination with nivolumab for metastatic Non-Small Cell Lung Cancer (NSCLC), Microsatellite Instability-High (MSI-H)/ Mismatch Repair Deficient (dMMR) Metastatic colorectal cancer, and unresectable Malignant Pleural Mesothelioma (MPM).

History of changes in PMDA indication

Colorectal cancer

• 2020-09-25: new indication for the treatment of unresectable advanced or recurrent microsatellite instability-high (MSI-High) colorectal cancer that has progressed after cancer chemotherapy.

Esophageal cancer

• 2022-05-26: New indication and a new dosage for the treatment of unresectable advanced or recurrent esophageal cancer.

Malignant pleural mesothelioma

• 2021-05-27: new indication and a new dosage for the treatment of unresectable advanced or recurrent malignant pleural mesothelioma.

Non-small cell lung cancer

• 2020-11-27: new indication and a new dosage for the treatment of unresectable advanced or recurrent non-small cell lung cancer.

Also known as

• Code names: BMS-734016, MDX-010
• Brand name: Yervoy