The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of ipilimumab (Yervoy) for the treatment of pediatric patients aged 12 years and older with unresectable or metastatic melanoma, according to Bristol-Myers Squibb (BMS), the manufacturer of the CTLA-4 inhibitor.
The application 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 European Commission (EC) will now review the application and make its final decision. According to BMS, the CHMP recommendation is its first positive opinion for an immuno-oncology agent in the pediatric setting.
“Pediatric melanoma is a particularly rare cancer, with limited treatment options for children in the EU impacted by the disease,” Murdo Gordon, executive vice president and chief commercial officer, BMS, said in a press release. “We are pleased with today’s positive CHMP opinion and look forward to hearing from the EC, as we continue to develop and deliver new therapies for the pediatric cancer community.”
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.”
The FDA approved ipilimumab for pediatric melanoma in July 2017, based on the same data. The approved ipilimumab dose for pediatric melanoma patients is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for 4 doses.
The recombinant, human monoclonal antibody ipilimumab binds to CTLA-4, a negative regulator of T-cell activity, and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Research has demonstrated that blocking CTLA-4 enhances T-cell activation and proliferation, including tumor infiltrating T-effector cells. An additional effect of CTLA-4 inhibition is reducing T-regulatory cell function, which potentially enhances T-cell responsiveness, including an immune response against the tumor.
Ipilimumab is approved in more than 50 countries for the treatment of patients with unresectable or metastatic melanoma.