General Information

Yervoy (ipilimumab) is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a molecule on T cells that suppresses the immune response. Blockade of CTLA-4 augments T-cell activation and proliferation and ipilimumab works via T-cell mediated anti-tumor immune responses.

Yervoy is specifically indicated for the treatment of unresectable or metastatic melanoma.

Yervoy is supplied as a solution for intravenous administration. The recommended dose of Yervoy is 3 mg/kg administered intravenously over 90 minutes every three weeks for a total of four doses.

Clinical Results

FDA Approval
The FDA approval of Yervoy was based on a randomized, double-blind, double-dummy study in 676 previously treated subjects with unresectable or metastatic melanoma. The subjects received Yervoy alone, Yervoy plus an investigational peptide vaccine gp100, or the gp100 vaccine alone. Yervoy was administered at 3 mg/kg as an intravenous infusion every three weeks for four doses. Gp100 was administered at a dose of 2 mg peptide by deep subcutaneous injection every three weeks for four doses. The primary endpoint was overall survival in the Yervoy plus gp100 arm versus the gp100 monotherapy arm. Assessment of tumor response to Yervoy was conducted at weeks 12 and 24, and every three months thereafter. Survival rate at 1 year was 46% in the Yervoy arm vs. 25% in the gp100 arm. The estimated survival rate at 2 years was 24% in the Yervoy arm vs. 14% in the gp100 arm. Subjects treated with Yervoy had a 34% reduction in the risk of death over the gp100 control arm and those treated with Yervoy plus gp100 had a 32% reduction in the risk of death over the gp100 control arm. Median overall survival was 10, 10 and 6 months for the Yervoy alone, Yervoy + gp100 arm and gp100 alone arms, respectively.

Side Effects

Adverse events associated with the use of Yervoy may include, but are not limited to, the following:

• fatigue
• diarrhea
• pruritus
• rash
• colitis

Mechanism of Action

Yervoy (ipilimumab) is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a molecule on T cells that suppresses the immune response. CTLA-4 is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.

Literature References

Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ Improved survival with ipilimumab in patients with metastatic melanoma New England Journal of Medicine 2010 Aug 19;363(8):711-23

O'Day SJ, Maio M, Chiarion-Sileni V, Gajewski TF, Pehamberger H, Bondarenko IN, Queirolo P, Lundgren L, Mikhailov S, Roman L, Verschraegen C, Humphrey R, Ibrahim R, de Pril V, Hoos A, Wolchok JD Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Annals of Oncology : Official Journal of the European Society for Medical Oncology 2010 Aug;21(8):1712-7

Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, Snively J, Hersh E Phase I/II study of ipilimumab for patients with metastatic melanoma. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 2008 Dec 20;26(36):5950-6

Additional Information

For additional information regarding Yervoy or metastatic melanoma, please visit the Yervoy web page.