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 [7] (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 [5]. 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 [2], based on results from the CheckMate 214 trial (NCT02231749) [6].

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 Trials
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

External links

For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA)