Unknown

Dataset Information

0

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


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/m2, 600 mg/m2, and 800 mg/m2 once daily for 28-day cycles (C) was used. Response was assessed at regular intervals. Pharmacokinetics and population pharmacokinetics were analyzed during C1.

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.

SUBMITTER: Boal LH 

PROVIDER: S-EPMC7909006 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9629437 | biostudies-literature
| S-EPMC5508592 | biostudies-literature
| S-EPMC8275010 | biostudies-literature
| S-EPMC7332409 | biostudies-literature
| S-EPMC6373434 | biostudies-literature
| S-EPMC5794522 | biostudies-literature
| S-EPMC5380388 | biostudies-literature
| S-EPMC3524754 | biostudies-literature
| S-EPMC8141405 | biostudies-literature
| S-EPMC4713719 | biostudies-literature