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Updated: Jun 15, 2026

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
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A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric and Young Adult

Filemon S Dela Cruz1, Elizabeth Fox2, Steven G DuBois3

  • 1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Pediatric Blood & Cancer
|May 2, 2025
PubMed
Abstract

Insights

Lenvatinib plus everolimus showed a manageable safety profile in pediatric patients with solid tumors. While efficacy endpoints were not met, some antitumor activity was observed in Ewing sarcoma and rhabdomyosarcoma.

Area of Science:

  • Pediatric Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Developing targeted therapies with manageable toxicities is crucial for pediatric cancer treatment.
  • Lenvatinib and everolimus are targeted agents with potential in solid tumors.

Purpose of the Study:

  • To determine the recommended Phase 2 dose (RP2D) of lenvatinib plus everolimus in pediatric patients.
  • To evaluate the antitumor activity and safety of this combination in children and young adults with recurrent/refractory solid tumors.

Main Methods:

  • Phase 1 utilized a rolling-six design to establish the maximum tolerated dose (MTD) and RP2D.
  • Phase 2 enrolled patients aged 2-21 with Ewing sarcoma, rhabdomyosarcoma, or high-grade glioma.
  • Primary endpoints included MTD, RP2D, safety, and objective response rate (ORR) at Week 16.

Main Results:

  • The MTD and RP2D were determined to be lenvatinib 11 mg/m² plus everolimus 3 mg/m² daily.
  • Two partial responses were observed in patients with rhabdomyosarcoma; two patients with Ewing sarcoma had prolonged disease control.
  • The safety profile was manageable and consistent with that observed in adult populations.

Conclusions:

  • Lenvatinib plus everolimus demonstrates a manageable safety profile in pediatric patients with select solid tumors.
  • Although overall efficacy endpoints were not met, observed antitumor activity in specific subtypes warrants further investigation.
Keywords:
Ewing sarcomaeverolimushigh‐grade gliomalenvatinibpediatric solid tumorsrhabdomyosarcoma

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