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Boal LH, Glod J, Spencer M, et al. Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I-Related Plexiform Neurofibromas. Clin Cancer Res. 2020;26(23):6112-6121doi: 10.1158/1078-0432.CCR-20-1696.
Boal, L. H., Glod, J., Spencer, M., Kasai, M., Derdak, J., Dombi, E., Ahlman, M., Beury, D. W., Merchant, M. S., Persenaire, C., Liewehr, D. J., Steinberg, S. M., Widemann, B. C., & Kaplan, R. N. (2020). Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I-Related Plexiform Neurofibromas. Clinical cancer research : an official journal of the American Association for Cancer Research, 26(23), 6112-6121. https://doi.org/10.1158/1078-0432.CCR-20-1696
Boal, Lauren H, et al. "Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I-Related Plexiform Neurofibromas." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 26,23 (2020): 6112-6121. doi: https://doi.org/10.1158/1078-0432.CCR-20-1696
Boal LH, Glod J, Spencer M, Kasai M, Derdak J, Dombi E, Ahlman M, Beury DW, Merchant MS, Persenaire C, Liewehr DJ, Steinberg SM, Widemann BC, Kaplan RN. Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I-Related Plexiform Neurofibromas. Clin Cancer Res. 2020 Dec 01;26(23):6112-6121. doi: 10.1158/1078-0432.CCR-20-1696. Epub 2020 Sep 17. PMID: 32943455; PMCID: PMC7909006.
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Clin Cancer Res. 2020 Dec 01;26(23):6112-6121. doi: 10.1158/1078-0432.CCR-20-1696. Epub 2020 Sep 17.

Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I-Related Plexiform Neurofibromas.

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

Lauren H Boal, John Glod, Melissa Spencer, Miki Kasai, Joanne Derdak, Eva Dombi, Mark Ahlman, Daniel W Beury, Melinda S Merchant, Christianne Persenaire, David J Liewehr, Seth M Steinberg, Brigitte C Widemann, Rosandra N Kaplan

Affiliations

  1. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  2. Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, D.C.
  3. Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
  4. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  5. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. [email protected].

PMID: 32943455 PMCID: PMC7909006 DOI: 10.1158/1078-0432.CCR-20-1696

Abstract

PURPOSE: Simultaneously targeting the tumor and tumor microenvironment may hold promise in treating children with refractory solid tumors. Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant cell tumor. A phase I trial was conducted in pediatric and young adult patients with refractory leukemias or solid tumors including neurofibromatosis type 1-related plexiform neurofibromas.

PATIENTS AND METHODS: A rolling six design with dose levels (DL) of 400 mg/m

RESULTS: Twelve patients (4 per DL, 9 evaluable) enrolled on the dose-escalation phase and 4 patients enrolled in the expansion cohort: median (lower, upper quartile) age 16 (14, 16.5) years. No dose-limiting toxicities were observed. Pharmacokinetics appeared linear over three DLs. Pharmacokinetic modeling and simulation determined a weight-based recommended phase II dose (RP2D). Two patients had stable disease and 1 patient with peritoneal mesothelioma (C49+) had a sustained partial response (67% RECIST reduction). Pharmacodynamic markers included a rise in plasma macrophage CSF (MCSF) levels and a decrease in absolute monocyte count.

CONCLUSIONS: Pexidartinib in pediatric patients was well tolerated at all DL tested, achieved target inhibition, and resulted in a weight-based RPD2 dose.

©2020 American Association for Cancer Research.

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