Phase 1/2 study of liposomal irinotecan plus S-1 for metastatic pancreatic cancer refractory to gemcitabine-based treatment
- PMID: 40252631
- DOI: 10.1016/j.ejca.2025.115424
Phase 1/2 study of liposomal irinotecan plus S-1 for metastatic pancreatic cancer refractory to gemcitabine-based treatment
Abstract
Background: Liposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) improves survival in gemcitabine-refractory metastatic pancreatic cancer (PC) but requires a central venous port. S-1, an oral fluoropyrimidine with proven efficacy in PC, may replace 5-FU/LV in nal-IRI plus 5-FU/LV, potentially enhancing both convenience and antitumor effect.
Methods: This single-arm, open-label, phase 1/2 study included patients with histologically or cytologically confirmed adenocarcinoma, aged 20-80 years, an Eastern Cooperative Oncology Group performance status of 0-1, with metastatic disease, and refractory to gemcitabine-based treatment. The primary endpoint in phase 1 part was the frequency of dose-limiting toxicity (DLT) to nal-IRI plus S-1. The primary endpoint in phase 2 part was overall survival. This trial was registered in the Japan Registry of Clinical Trials database (jRCTs031210040).
Results: In phase 1 part, one patient with DLT was observed at nal-IRI 70 mg/m2 (day 1) with S-1 80 mg/m2/day (day 1-7) in a 2-week cycle, establishing this as the recommended phase 2 dose (RP2D). Forty-nine patients from phase 1 (n = 6) and phase 2 part (n = 43) were treated with the RP2D, and their results were pooled. Median overall survival was 10.3 months (95 % confidence interval, 8.1-12.0 months). A confirmed partial response was achieved in 10 patients (20.4 %). The most frequent treatment-emergent adverse events were hypoalbuminemia (98.0 %), anemia (98.0 %), and anorexia (81.6 %). There were no treatment-related deaths.
Conclusions: This study demonstrated that nal-IRI plus S-1 exhibited promising efficacy and an acceptable safety profile in patients with metastatic PC refractory to gemcitabine-based treatment.
Keywords: Chemotherapy; Gemcitabine; Liposomal irinotecan; Pancreatic cancer; Phase 1/2 study; Refractory; S-1; Second-line.
Copyright © 2025 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroshi Imaoka has received research funding from Ono Pharmaceutical, Les Laboratoires Servier, Novartis, and Boehringer Ingelheim; and honoraria from Les Laboratoires Servier, Yakult Honsha, Boston Scientific, Kaneka Medix, Medico’s Hirata, SB KAWASUMI LABORATORIES, AstraZeneca, and Novartis; and payment expert testimony from Kaneka Medix; and is a member of Data Safety Monitoring Board or advisory board for Les Laboratoires Servier. Masafumi Ikeda has received research funding from Boehringer Ingelheim, Delta-Fly Pharma, Merus N.V, Invitae, Les Laboratoires Servier, and Novartis; and consulting fees from Astellas, Les Laboratoires Servier, and Novartis; and honoraria from Guardant Health Japan, Les Laboratoires Servier, Taiho Pharmaceutical, MSD, Nippon Kayaku, Yakult Honsha. Naohiro Okano has received honoraria from Taiho Pharmaceutical, Eisai, Bayer, Chugai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, MSD, Incyte, and Les Laboratoires Servier. Satoshi Kobayashi has received honoraria from AstraZeneca, MSD, Les Laboratoires Servier, Taiho Pharmaceutical, and Yakult Honsha. Shuichi Mitsunaga has received research funding from Chugai Pharmaceutical, TORAY industries, Ajinomoto, Astellas Pharma, Ono Pharmaceutical, PFDeNA, Mitsui Chemicals, and Pfizer; and royalties or licenses from Mitsui Chemicals; and consulting fees from Pfizer; and honoraria from Ono Pharmaceutical, Astellas, AstraZeneca, Otsuka Pharmaceutical, and Meiji Seika Pharma; and has patents planned, issued, or pending in collaboration with Ajinomoto, and Chugai Pharmaceutical. Takaaki Furukawa has received honoraria from Novartis, and Chugai Pharmaceutical. Satoshi Hamauchi has received honoraria from Ono Pharmaceutical. Makoto Ueno has received research funding from Taiho Pharmaceutical, AstraZeneca, MSD, Les Laboratoires Servier, Ono Pharmaceutical, Incyte, Chugai Pharmaceutical, Boehringer Ingelheim, Eisai, Novartis, Astellas, J-pharma, Delta Fly Pharma, Novocure, and Chiome; and honoraria from Taiho Pharmaceutical, AstraZeneca, Yakult Honsha, MSD, Les Laboratoires Servier, Ono Pharmaceutical, Incyte, Chugai Pharmaceutical, Boehringer Ingelheim, J-pharma, Daiichi Sankyo, Eisai, Takeda Pharmaceutical, and Novartis. Junji Furuse has received honoraria from Ono Pharmaceutical, Chugai Pharmaceutical, Eisai, AstraZeneca, Les Laboratoires Servier, MSD, Novartis, Takeda, Taiho Pharmaceutical, Teijin, Daiichi Sankyo, Incyte, Ohhara Pharmaceutical, J-Pharma, Astellas, Onco Therapy Science, Delta-Fly-Pharma, Pfizer, TME Therapeutics, Fuji film, Terumo, Eli Lilly, Bayer, and EA Pharma; and is a member of Data Safety Monitoring Board or advisory board for Onco Therapy Science, Chugai Pharmaceutical, Astellas, AstraZeneca, Takara bio, Merck, MSD, and Taiho Pharmaceutical. The other authors have no conflict of interest.
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