A phase 1/2 study of lenvatinib in combination with everolimus in recurrent and refractory pediatric and young adult solid tumors Journal Article

  


Authors: Dela Cruz, F. S.; Fox, E.; DuBois, S. G.; Friedman, G. K.; Croop, J. M.; Kim, A.; Morgenstern, D. A.; Balis, F. M.; Macy, M. E.; Pressey, J. G.; Watt, T.; Krystal, J. I.; Vo, K. T.; Mody, R.; Laetsch, T. W.; Weigel, B. J.; O'Hara, K.; He, C. S.; Aluri, J.; Okpara, C. E.; Glade Bender, J. L.
Article Title: A phase 1/2 study of lenvatinib in combination with everolimus in recurrent and refractory pediatric and young adult solid tumors
Abstract: Introduction: Developing targeted therapies with manageable toxicities remains a high priority for pediatric cancer. We sought to determine the recommended Phase 2 dose (RP2D) and evaluate the antitumor activity of lenvatinib+everolimus in children/young adults with select recurrent/refractory solid tumors. Methods: Patients 2–21 years old were eligible. Phase 1 used a rolling-six design. Phase 2 was limited to patients with Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), or high-grade glioma (HGG), and ≤2 prior VEGF/VEGFR-targeted therapies. Primary endpoints included the determination of maximum tolerated dose (MTD), RP2D, safety/toxicity (Phase 1), and objective response rate (ORR) per RECIST version 1.1 (RANO for HGG) at Week 16 (Phase 2). Results: In Phase 1, 23 patients received lenvatinib 11 mg/m2 (dose level [DL] 1, n = 18) or 8 mg/m2 (DL −1, n = 5) combined with everolimus 3 mg/m2 orally once daily. DL1 was declared the MTD/RP2D given dose-limiting toxicities (proteinuria [n = 1]; hypertriglyceridemia and hypercholesterolemia [n = 1]) observed in two of 12 patients treated at DL1. In Phase 2, 41 patients (EWS, n = 10; RMS, n = 20; HGG, n = 11) were treated with the RP2D. Two patients with RMS experienced partial response by Week 16. No other objective responses were observed. Two patients with EWS experienced prolonged disease control (≥23 weeks). No new safety signals were identified. The safety profile was similar to those of treated adults with renal cell carcinoma. Conclusion: Lenvatinib+everolimus has a manageable safety profile in this pediatric population. Despite unmet efficacy endpoints, the antitumor activity observed in RMS and EWS may warrant further study in select pediatric solid tumors. ClinicalTrials.gov number: NCT03245151. © 2025 Eisai Inc and The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.
Keywords: ewing sarcoma; rhabdomyosarcoma; everolimus; high-grade glioma; pediatric solid tumors; lenvatinib
Journal Title: Pediatric Blood and Cancer
Volume: 72
Issue: 7
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2025-07-01
Start Page: e31692
Language: English
DOI: 10.1002/pbc.31692
PUBMED: 40313040
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-105004217533&doi=10.1002%2fpbc.31692&partnerID=40&md5=51e153865ca5c92689d48b16c6563a18
Notes: Article -- Source: Scopus
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MSK Authors
  1. Filemon Dela Cruz
    62 Dela Cruz
  2. Julia L Glade Bender
    85 Glade Bender
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