Data from Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors

Abstract

<div>Abstract<p><b>Purpose:</b> Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol.</p><p><b>Experimental Design:</b> This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects ≤21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m<sup>2</sup> 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 toxicity.</p><p><b>Results:</b> Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (<i>n</i> = 12), sarcoma (<i>n</i> = 17), or other refractory solid tumors (<i>n</i> = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities 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 (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma).</p><p><b>Conclusions:</b> Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance. <i>Clin Cancer Res; 22(6); 1364–70. ©2015 AACR</i>.</p></div>