134TiP - A phase I/II study of nanoliposomal irinotecan plus S-1 in metastatic pancreatic cancer after first-line gemcitabine-based chemotherapy

Background

S-1, an oral fluoropyrimidine anticancer drug, showed promising results in patients with unresectable pancreatic cancer (PC) in a phase 3 study (Ueno, 2013). Thus, the nanoliposomal irinotecan (nal-IRI)/S-1 regimen, replacing 5-FU/LV in the nal-IRI+5-FU/LV regimen with S-1, not only improves the convenience of treatment with no requirement of intravenous port system, but it is also expected to exert stronger anticancer effects. Thus, a phase 1/2 study to evaluate the safety and efficacy of nal-IRI/S-1 for the treatment of metastatic PC after previous gemcitabine-based chemotherapy was conducted.

Trial design

The phase 1 part used a conventional 3+3 dose-escalation design. The primary endpoint in the phase 1 part was the frequency of dose-limiting toxicities (DLTs). Intravenous nal-IRI was administered on day 1, and oral S-1 was administered on days 1-7 of a 14-day course. The DLT-assessment period was 2 cycles at each dose level. Adverse events (AEs) were assessed based on CTCAE v5.0. A total of 12 patients were assigned to 3 dose levels: 3 patients were at level 1 (nal-IRI, 60 mg/m²; S-1, 60-100 mg/day), 3 at level 2 (nal-IRI, 60 mg/m²; S-1, 80-120 mg/day), and 6 at level 3 (nal-IRI, 70 mg/m²; S-1, 80-120 mg/day). DLT was observed in 1 patient at level 3 (grade 3 anorexia). The recommended dose (RD) was determined to be nal-IRI of 70 mg/m², with S-1 of 80-120 mg/day. The most common grade 3-4 hematological AEs included neutropenia (8.3%), and the most common grade 3-4 non-hematological AE was anorexia (16.7%). The RD was determined to be 70 mg/m² of nal-IRI combined with 80-120 mg/day of S-1. The phase 2 part has recently started accrual.

Clinical trial identification

jRCTs031210040.

Legal entity responsible for the study

The authors.

Funding

Servier.

Disclosure

H. Imaoka: Financial Interests, Personal, Invited Speaker: Yakult Honsha, AstraZeneca, Nihon Servier, Kaneka; Financial Interests, Personal, Advisory Board: Nihon Servier; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceutical. M. Ueno: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, AstraZeneca, MSD, Nihon Servier, Ono Pharmaceutical, Incyte, Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Taiho Pharmaceutical, AstraZeneca, Merck Biopharma, MSD, Astellas Pharma, Eisai, Ono Pharmaceutical, Incyte, Chugai Pharmaceutical, DFP, Daiichi Sankyo. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yaklut, MSD, Incyte, Ono, Bayer. S. Kobayashi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Bayer Yakuhin, Eisai Pharmaceutical, Yakult Honsha, Servier Japan, GlaxoSmithKlein, Chugai Pharmaceutical, Eli Lilly Japan, Takeda Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Ono, Takeda, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, ASLAN, Chugai, Nihon Servier, Takeda; Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Serono, MSD, Ono, Yakult, Novartis, Takeda, J-Pharma, Pfizer, Chiome Bioscience, NIHON Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V. All other authors have declared no conflicts of interest.