Phase I Clinical Trial of Ipilimumab in Pediatric XXXX with @entity5 .

@entity1 @entity788 @entity137 @entity242 @entity55 @entity5 @entity1352 @entity1960 @entity2744 @entity421 @entity14495 @entity320
PURPOSE: Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of @entity320 but not studied in @entity1 until this phase I protocol. EXPERIMENTAL DESIGN: This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects <= 21 years old with recurrent or progressive @entity5 . Dose escalation cohorts received 1, 3, 5, or 10 mg/m(2) intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable @entity137 . RESULTS: Thirty-three @entity1 received 72 doses of ipilimumab. @entity1 enrolled had @entity320 (n = 12), @entity242 (n = 17), or other refractory @entity5 (n = 4). Immune-related adverse events included @entity788 , @entity55 , @entity1960 , @entity2744 , and transaminitis with dose-limiting @entity137 observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles ( @entity320 , @entity421 , @entity14495 , and @entity1352 ). CONCLUSIONS: Ipilimumab was safely administered to pediatric @entity1 using management algorithms for immune-related @entity137 . The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric @entity137 were evident after a single dose. Although no objective @entity5 regressions were observed with ipilimumab as a single agent, subjects with immune-related @entity137 had an increased overall survival compared with those who showed no evidence of breaking tolerance.
