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Clin Cancer Res. 2016 Mar 15;22(6):1364-70. doi: 10.1158/1078-0432.CCR-15-0491. Epub 2015 Nov 3.

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

Author information

1
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. mackallc@mail.nih.gov.
2
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
3
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY and Weill-Cornell Medical College, New York, NY.
4
Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA.
5
National Institute of Child Health and Human Development, NIH, Bethesda, MD.
6
National Eye Institute, NIH, Bethesda, MD.
7
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Weill-Cornell Medical College, New York, NY.
8
Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD.

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.

PMID:
26534966
PMCID:
PMC5027962
DOI:
10.1158/1078-0432.CCR-15-0491
[Indexed for MEDLINE]
Free PMC Article

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