Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma

Yun Liu, Bo Zhang, Jianping Xu, Xingyuan Wang, Jialin Tang, Jing Huang, Yun Liu, Bo Zhang, Jianping Xu, Xingyuan Wang, Jialin Tang, Jing Huang

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/m2). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m2. 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/m2. 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.

Conflict of interest statement

The author(s) declare that they have no conflict of interest.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Figures

Fig. 1
Fig. 1
Response to the study treatment. a Waterfall plot of best percent change in target lesions from baseline. The star indicates a patient with a new lesion despite stable target lesions. b Percentage change of target lesions from baseline
Fig. 2
Fig. 2
Mean plasma concentration–time curve with positive standard deviations (SDs). a Total irinotecan, b free irinotecan, c SN-38 and d SN-38G at 30, 60, 90 and 120 mg/m2 dose levels of LY01610

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