Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors Journal Article
| Authors: | Merchant, M. S.; Wright, M.; Baird, K.; Wexler, L. H.; Rodriguez-Galindo, C.; Bernstein, D.; Delbrook, C.; Lodish, M.; Bishop, R.; Wolchok, J. D.; Streicher, H.; Mackall, C. L. |
| Article Title: | 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/m2 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. Clin Cancer Res; 22(6); 1364-70. © 2015 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 22 |
| Issue: | 6 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2016-03-15 |
| Start Page: | 1364 |
| End Page: | 1370 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-15-0491 |
| PROVIDER: | scopus |
| PUBMED: | 26534966 |
| PMCID: | PMC5027962 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2016 -- Source: Scopus |
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