About FDA


On March 25, 2011, the U. S. Food and Drug Administration approved ipilimumab injection (YERVOY, Bristol-Myers Squibb Company) for the treatment of unresectable or metastatic melanoma.

The approval was based on a randomized (3:1:1), double-blind, double-dummy clinical trial (MDX010-20) in patients with unresectable or metastatic melanoma who had received at least one prior systemic treatment for melanoma. Overall survival (OS) was the trial’s primary endpoint. Progression-free survival and best overall response rate were also assessed.

The clinical trial enrolled 676 patients with HLA-A2*0201 positive genotype. This HLA-A2*0201 genotype facilitated the immune presentation of the investigational tumor vaccine. The three treatment arms consisted of ipilimumab, 3 mg/kg intravenously, in combination with the tumor vaccine (n=403), ipilimumab plus vaccine placebo (n=137), and tumor vaccine with placebo (n=136). The trial excluded patients with active autoimmune disease or those receiving systemic immunosuppression for organ transplantation.

The median age of patients was 57 years with 29% of patients age 65 years or older. More than half the patients were male, 71% had M1c stage, 12% had histories of previously treated brain metastases, 98% had ECOG performance status of either 0 or 1, and 23% had received prior aldesleukin (IL-2).

Overall survival was longer with ipilimumab alone compared to tumor vaccine [HR 0.66 (95% CI: 0.51, 0.87), p=0.0026] with median OS of 10 and 6 months, respectively, for ipilimumab alone and the vaccine arm. The trial also demonstrated a statistically significant improvement in OS for the combination of ipilimumab plus tumor vaccine compared to tumor vaccine alone [HR 0.68 (95% CI: 0.55, 0.85), p= 0.0004, log-rank test)] with median OS of 10 and 6 months, respectively. The best overall response rate (investigator assessed) was 10.9% (95% CI: 6.3%, 17.4%) in the ipilimumab arm, 5.7% (95% CI: 3.7%, 8.4%) in the combination of ipilimumab plus vaccine arm, and 1.5% (95% CI: 0.2%, 5.2%) in the vaccine arm.

Safety data was evaluated in 511 patients who received ipilimumab alone or in combination with the tumor vaccine. The most common (>5%) adverse reactions (AEs) were manifestations of ipilimumab’s immunological mechanism of action leading to T-cell activation and proliferation. Such immune-mediated adverse reactions included diarrhea, pruritus, rash, and colitis. The most serious AEs were also immune-mediated adverse reactions. Ipilimumab was discontinued for adverse reactions in 10% of patients. Thirteen percent of ipilimumab treated patients experienced a high grade immune-mediated AE. The most common of these involved the colon, liver, skin, endocrine system, and nervous system. Management of immune-mediated AEs may include discontinuation of ipilimumab and initiation of high dose corticosteroids.

The recommended dose and schedule for ipilimumab is 3 mg/kg as an intravenous infusion every 3 weeks for a total of four doses.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125377s0000lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Page Last Updated: 11/27/2015
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