Abstract
PURPOSE: This phase I trial was performed to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), preliminary efficacy, and pharmacokinetics (PK) of LY01610, a novel liposome-encapsulated irinotecan, in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: This trial was conducted in two stages. In the dose-escalation stage, patients with advanced ESCC refractory or intolerant to previous chemotherapy received escalating doses of LY01610. A recommended dose based on patient tolerance was then expanded in the second stage. LY01610 was administered intravenously every 2 weeks, except that the first cycle in dose escalation was 3 weeks to allow observation of DLTs. RESULTS: Twenty-four patients were enrolled across 4 dose levels (30, 60, 90 and 120 mg/m(2)). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m(2). The most common grade 3/4 adverse events were leukopenia in six patients (25.0%), anemia in six patients (25.0%) and neutropenia in five patients (20.8%). One patient achieved complete response, and four had partial response, including one patient receiving LY01610 at the starting dose of 30 mg/m(2). Compared with conventional irinotecan, the PK profile of LY01610 was characterized by increased and prolonged exposure of total irinotecan and the active metabolite SN-38 in plasma. CONCLUSION: LY01610 demonstrated manageable toxicity and promising anti-tumor activity in patients with advanced ESCC. Future clinical development of LY01610 as single agent or in combination with other anti-cancer agents in treating ESCC patients is warranted. TRIAL REGISTRATION: NCT04088604 at ClinicalTrials.gov.