- Guide to PHARMACOLOGY
Synonyms: MDX-010 | MDX-101 | MDX-CTLA-4 | Yervoy®
ipilimumab is an approved drug (FDA and EMA (2011))
Compound class: Antibody
Comment: Ipilimumab is an anti-CTLA-4 monoclonal antibody. It is likely the subject of patent WO2001014424 , as antibody 10D1 which was investigated further, claimed in patent EP1503794 . Ipilimumab is an immune checkpoint inhibitor.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|Ipilimumab is used to treat metastatic or unresectable melanoma. Accelerated FDA approval has been granted (September 2015) for a combination anti-melanoma therapy containing ipilimumab and nivolumab for patients with BRAF V600 wild-type, unresectable or metastatic melanoma [3,5]. In October 2015, the FDA extended approval to include using ipilimumab as adjuvant treatment for patients with stage III melanoma, to reduce the risk of tumour recurrence after complete surgical resection, including total lymphadenectomy.
Combination therapy with ipilimumab and nivolumab has been reported to exhibit >60% objective-response rate (ORR) in treatment-naive advanced melanoma patients with BRAF wild-type tumours  (results from Phase 1 study NCT01927419). This is in comparison to ipilimumab alone which provided only 11% confirmed ORR. These findings have been confirmed by Phase 3 study (NCT01844505) results showing significantly longer progression-free survival in patients given the combination therapy vs. the nivolumab only group .
In July 2017, the FDA approved use of ipilimumab (3 mg/kg i.v. over 90 minutes every three weeks for a total of four doses) in pediatric patients (12 years and over) with unresectable or metastatic melanoma.
A combination therapy of nivolumab plus ipilimumab was granted FDA approval in April 2018, for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma , based on results from the CheckMate 214 trial (NCT02231749) .
|Mechanism Of Action and Pharmacodynamic Effects|
|Binds to cytotoxic T lymphocyte antigen 4 (CTLA-4), leading to inhibition of its inhibitory signal, and enhancing the ability of cytotoxic T lymphocytes to destroy cancer cells.|
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT01844505||Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)||Phase 3 Interventional||Bristol-Myers Squibb|
|NCT01927419||Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma||Phase 2 Interventional||Bristol-Myers Squibb|
|NCT02231749||Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)||Phase 3 Interventional||Bristol-Myers Squibb|
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)