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

ABSTRACT: PURPOSE: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. EXPERIMENTAL DESIGN: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(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 toxicity. RESULTS:Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 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). CONCLUSIONS: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.

SUBMITTER: Merchant MS

PROVIDER: S-EPMC5027962 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Merchant Melinda S MS Wright Matthew M Baird Kristin K Wexler Leonard H LH Rodriguez-Galindo Carlos C Bernstein Donna D Delbrook Cindy C Lodish Maya M Bishop Rachel R Wolchok Jedd D JD Streicher Howard H Mackall Crystal L CL

Clinical cancer research : an official journal of the American Association for Cancer Research 20151103 6

<h4>Purpose</h4>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.<h4>Experimental design</h4>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(2) intravenously every 3 weeks in a 3 + 3 design. Respons ...[more]

PMID: 26534966

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

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

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