A phase I study of liposomal Irinotecan (ONIVYDE®) in combination with TAS-102 (LONSURF®) in refractory solid tumors.
Journal
Investigational new drugs
Journal Volume
43
Journal Issue
3
Start Page
709
End Page
718
ISSN
1573-0646
Date Issued
2025-06-04
Author(s)
Chiang, Nai-Jung
Bai, Li-Yuan
Ho, I-Wei
Chiu, Chang-Fang
Lin, Ching-Chan
Chang, Kwang-Yu
Chen, Shang-Hung
Tsai, Hui-Jen
Lin, Yu-Ping
Chen, Li-Tzong
Abstract
Onivyde, a liposome-encapsulated irinotecan, is used for advanced pancreatic, while TAS-102 (trifluridine/tipiracil) is indicated for metastatic colorectal and gastric cancers. This study aims to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profiles of liposomal irinotecan combined with TAS-102. This multicenter, phase I study utilized a 3 + 3 dose-escalation design. Patients with treatment-refractory solid malignancies received free base liposomal irinotecan at 50-70 mg/m on Day 1 and TAS-102 at 25-35 mg/m twice daily on Days 1-5 of a 14-day cycle. Patients homozygous for UGT1A1*28 (TA7/TA7), UGT1A1*6 (A/A), or double heterozygous (TA6/TA7 and G/A) alleles were excluded. Prophylactic G-CSF was allowed. Twenty-six evaluable patients were enrolled across seven dose levels of liposomal irinotecan (free-base)/TAS-102 combination: 3 patients each at level 1 (50/25 mg/m), level 2A (60/25 mg/m), level 2B (50/30 mg/m), and level 3 (60/30 mg/m); 6 at level 4A (70/30 mg/m); 3 at level 4B (60/35 mg/m); and 5 at level 5 (70/35 mg/m). An additional 15 patients were enrolled in the expansion cohort at the MTD of 70/30 mg/m (level 4A), designated as the RP2D. Overall grade 3-4 treatment-related adverse events occurred in 44.2% of 43 all treated patients, with neutropenia (16.3%), diarrhea (14%), and fatigue (11.6%). Partial responses were observed in 18.4% of patients, predominantly in neuroendocrine tumor, gastric and esophageal carcinomas. The combination of liposomal irinotecan and TAS-102 at the RP2D of 70/30 mg/m demonstrated acceptable safety and promising efficacy in refractory solid tumors, warranting further investigation.
Subjects
Efficacy
Liposomal irinotecan
Pharmacokinetics
Phase 1 clinical trial
Solid tumors
TAS-102
SDGs
Type
journal article