First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.

ABSTRACT: Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administered orally under fasting conditions at 5-240 mg/m² and 30-36 mg/m², respectively, in patients with advanced solid tumors. Safety, efficacy, and pharmacokinetics (PK) were evaluated. Results Seventy-six patients were enrolled. The MTD and RD were TAS-114 200 mg/m² plus S-1 36 mg/m² and TAS-114 240 mg/m² plus S-1 30 mg/m², respectively. Common treatment-related adverse events were anemia, lymphocytopenia, leukopenia

SUBMITTER: Doi T 

PROVIDER: S-EPMC6538570 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature