Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Single-agent dose-finding cohort of a phase 1/2 study of lenvatinib in children and adolescents with refractory or relapsed solid tumors (#152)

Nathalie Gaspar 1 , Soledad Gallego 2 , Rajkumar Venkatramani 3 , Stefan Bielack 4 , Michela Casanova 5 , Franco Locatelli 6 , Estelle Thebaud 7 , Charlotte Rigaud 1 , Samuel Abbou 1 , Marion Gambart 8 , Bruce Morland 9 , Isabelle Aerts 10 , Silvija Kraljevic 11 , Di Li 11 , Hina Maniar 12 , Seiichi Hayato 13 , Corina Dutcus 12 , John Bower 14 , Quentin Campbell-Hewson 15
  1. Institute Gustave Roussy, Villejuif, France
  2. University Hospital Vall d'Hebron, Barcelona, Spain
  3. Texa Children's Hospital, Houston, Texas, USA
  4. Klinikum Stuttgart-Olgahospital, Stuttgart Cancer Center, Stuttgart, Germany
  5. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  6. Bambino Gesu Children's Hospital, University of Pavia, Rome, Italy
  7. CHU Nantes, Nantes, France
  8. Children's Hospital CHU, Toulouse, France
  9. Birmingham Children's Hospital, Birmingham, UK
  10. Institut Curie, Paris, France
  11. Eisai Ltd, Hatfield, UK
  12. Eisai Inc., Woodcliff Lake, NJ, USA
  13. Eisai Co., Ltd, Tokyo, Japan
  14. Eisai Australia Pty Ltd, Melbourne, VIC, Australia
  15. North of England Principal Treatment Centre for Cancer in Children and Young People, Great North Children's Hospital, Newcastle upon Tyne, UK


Lenvatinib is an inhibitor of VEGFR 1‒3, FGFR 1‒4, PDGFRα, RET, and KIT. Lenvatinib is approved in adults for radioiodine-refractory differentiated thyroid cancer (DTC) and in combination with everolimus in patients with advanced renal cell carcinoma. We show results from the single-agent lenvatinib dose-finding part of a phase 1/2 study in children and adolescents with solid tumors.


Patients, aged 2 to ≤18 years, had any relapsed or refractory solid tumor, evaluable or measurable disease, <2 prior VEGF-targeted therapies, and adequate organ function. A starting dose of lenvatinib 11 mg/m2 was escalated with a time-to-event continual reassessment method. The primary endpoint was to determine the recommended dose (RD), and secondary objectives were best overall response (BOR), objective response rate, safety, and pharmacokinetics (PK).


Twenty-three pts enrolled (11 mg/m2: n=5, 14-mg/m2: n=11, 17-mg/m2: n=7). The most common tumors were rhabdomyosarcoma (n=5), Ewing sarcoma (n=4), and neuroblastoma (n=3). Three dose-limiting toxicities occurred in cycle 1 at 14 mg/m2 (increased alanine aminotransferase: 1; hypertension: 2). All patients had any-grade TEAEs (grade 3/4: 65%), with vomiting (52%), abdominal pain (48%), decreased appetite (48%), diarrhea (44%), and hypothyroidism (44%) being the most common. One patient discontinued lenvatinib due to lenvatinib-related hypertension. BOR was stable disease (n=10). Effect of age on oral clearance and central volume of distribution was not significant. Exposure was similar to that in adults. Lenvatinib 14 mg/m2/day was, therefore, identified as the RD. Updated cohort 1 data will be shown.


The lenvatinib RD in children and adolescents was similar to the adult dosage and showed a reasonable safety profile. PK did not differ significantly from that in adults. Phase 1b dose-finding study of lenvatinib in combination with chemotherapy in osteosarcoma and phase 2 lenvatinib monotherapy (RD 14 mg/m2) parts in DTC and osteosarcoma are ongoing.