Abstract
PURPOSE: This phase 1 study aimed to assess the tolerability, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of lenvatinib capsules in Japanese patients with solid tumors when administered orally up to 24 mg on a once-daily (QD) continuous schedule. METHODS: Patients were enrolled in one of the two sequential cohorts (20 or 24 mg) of lenvatinib on a 28-day cycle based on the conventional 3 + 3 dose escalation design. Adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Tolerability was judged based on dose-limiting toxicities (DLTs) during Cycle 1. The drug was defined as tolerable when the incidence of DLTs was less than 33 %. RESULTS: Nine patients received lenvatinib [20 mg (n = 3); 24 mg (n = 6)]. No DLTs were observed. The most common AEs were thrombocytopenia, blood thyroid stimulating hormone increased, and hypertension (89 %), followed by leukopenia, headache, and proteinuria (78 %). The area under the concentration-time curve and maximum observed concentration increased dose proportionally. The PK profiles were similar to those in non-Japanese phase 1 studies. One patient with leiomyosarcoma showed a partial response, and three patients have maintained stable disease for more than 6 months. CONCLUSIONS: The 24-mg QD continuous dose of lenvatinib was determined to be tolerable with encouraging anti-tumor activity in Japanese patients with solid tumors.