FDA Approves Ipilimumab for Pediatric Melanoma

The FDA has approved ipilimumab (Yervoy) for the treatment of patients aged ≥12 years with unresectable or metastatic melanoma, according to Bristol-Myers Squibb (BMS), the manufacturer of the CTLA-4 inhibitor.

The expanded indication for ipilimumab is based on data across 2 trials in which objective responses were observed in 2 of 17 patients aged ≥12 years with advanced melanoma. The responses included 1 partial response that lasted for 16 months.

The approved ipilimumab dose for pediatric melanoma patients is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for 4 doses.

“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,” Lia Gore, MD, University of Colorado School of Medicine and Children’s Hospital of Colorado, said in a statement. “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 pivotal ipilimumab pediatric trials included a dose-finding study involving 33 patients aged 2 to 21 years with relapsed/refractory solid tumors, and a single-arm, open-label trial that accrued 12 patients aged 12 to 16 years with stage III/IV melanoma, either previously treated or untreated.

In the dose-finding trial, the median age was 13 years, and 20 of the patients were at least 12 years old. Patients received ipilimumab intravenously at doses of 1, 3, 5, and 10 mg/kg over 90 minutes every 3 weeks for 4 doses, and then every 12 weeks thereafter until progression or discontinuation.

The 12 patients in the single-arm trial were administered intravenous ipilimumab at 3 mg/kg (n = 4) or 10 mg/kg (n = 8) over 90 minutes every 3 weeks for 4 doses.

According to BMS, the safety profile of ipilimumab in children and adolescent patients was comparable to the safety profile in adult patients. Additionally, BMS noted in a press release that, “Based on a population pharmacokinetic analysis using available pooled data from 565 patients from 4 phase II adult studies (N = 521) and 2 pediatric studies (N = 44), body weight normalized clearance of Yervoy is comparable between adult and pediatric subjects.”

“When my daughter was diagnosed with melanoma, our entire family was devastated,” Brenda Busby, mother to a 12-year-old patient and pediatric program coordinator, Melanoma Research Foundation, said in a statement. “As someone who has lived with the many challenges of pediatric cancer, I know how important it is for patients and their families who face metastatic melanoma to have access to new therapies.”

Also commenting on the expanded pediatric indication, Chris Boerner, PhD, president and head of US commercial operations, BMS, said, “Despite significant advancements in oncology research for adults in recent years, treatment options continue to be limited for pediatric patients with metastatic melanoma. At Bristol-Myers Squibb, we are committed to providing meaningful support to the pediatric oncology community. This latest approval of Yervoy exemplifies our ongoing effort to expand the availability of therapies for younger cancer patients.”

Ipilimumab was previous approved for adult patients with unresectable or metastatic melanoma, as well as for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.