Dataset Information

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

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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8143070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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