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.