FDA Expands Approval of Ipilimumab to Pediatric Patients 12 Years and Older


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On July 24, the U.S. Food and Drug Administration (FDA) expanded the indication for ipilimumab (Yervoy) injection for intravenous use now to include the treatment of unresectable or metastatic melanoma in pediatric patients 12 years of age and older. Ipilimumab was evaluated in 2 trials of pediatric patients: a dose-finding study in 33 patients aged 2 to 21 years with relapsed or refractory solid tumors, and an open-label, single-arm trial in 12 adolescents (aged 12–16 years) with previously treated or untreated, unresectable stage III or IV malignant melanoma.

The overall safety profile of ipilimumab in children and adolescents was consistent with the safety profile in adults, and similarities in disease between adult and pediatric patients 12 years and older allow for extrapolation of data. Based on a population pharmacokinetic analysis, exposure in adolescents aged 12 years and older is comparable to that in adults for the approved dose of 3 mg/kg, administered intravenously over 90 minutes every 3 weeks for a total of 4 doses.

Lia Gore, MD

Lia Gore, MD

“Metastatic melanoma is extremely rare in children and adolescents, which makes it particularly difficult to investigate in clinical trials. Though designing clinical trials in small pediatric populations can be challenging, this group of investigators committed to bringing a new therapy to those in need,” said Lia Gore, MD, of the University of Colorado School of Medicine and Children’s Hospital of Colorado. “Ipilimumab’s approval represents the culmination of a long effort and gives physicians the ability to expand immuno-oncology—one of the most exciting areas of medicine—for the treatment of young adults with metastatic melanoma.”

The expanded indication builds upon 6 years of experience with ipilimumab, which has been used to treat more than 38,000 adult patients with metastatic melanoma since its first approval.

“Despite significant advancements in oncology research for adults in recent years, treatment options continue to be limited for pediatric patients with metastatic melanoma,” said Chris Boerner, PhD, President and head of U.S. commercial operations, Bristol-Myers Squibb. “This latest approval of ipilimumab exemplifies our ongoing effort to expand the availability of therapies for younger cancer patients.”

Two Pediatric Studies

Ipilimumab has been evaluated in a total of 45 pediatric patients across 2 clinical trials. The use of ipilimumab in pediatric patients 12 years and older is supported by evidence from adequate and well-controlled studies of ipilimumab in adults and population pharmacokinetic data demonstrating that the exposure at a dose of 3 mg/kg in the pediatric and adult populations is comparable. In addition, the tumor biology and the course of advanced melanoma are sufficiently similar in adults and pediatric patients 12 years and older to allow extrapolation of data from adults to pediatric patients.

Chris Boerner, PhD

Chris Boerner, PhD

In a dose-finding trial, ipilimumab was evaluated in 33 pediatric patients with relapsed or refractory solid tumors. Patients enrolled in the study ranged from 2 to 21 years old, with a median age of 13 years. Twenty of the patients were aged 12 years or older. Ipilimumab was administered at doses of 1, 3, 5, and 10 mg/kg intravenously over 90 minutes every 3 weeks for 4 doses and then every 12 weeks thereafter until disease progression or treatment discontinuation.

Ipilimumab was also evaluated in an open-label, single-arm trial in 12 pediatric patients 12 years and older with previously treated or untreated, unresectable stage III or IV malignant melanoma. Patients received ipilimumab at 3 mg/kg (4 patients) or 10 mg/kg (8 patients) intravenously over 90 minutes every 3 weeks for 4 doses.

Of the 17 patients aged 12 years or older with melanoma treated with ipilimumab across both studies, 2 patients experienced objective responses, including 1 partial response that was sustained for 16 months.

Approved Labeling

The approved dose for ipilimumab in pediatric patients with unresectable or metastatic melanoma is 3 mg/kg, administered intravenously over 90 minutes every 3 weeks for a total of 4 doses.

The drug is associated with a boxed warning and may result in severe to fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. ■



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