First-line liposomal irinotecan in combination with 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (NALIRIFOX) showed promising antitumor activity in adult patients with unresectable, locally advanced or metastatic ductal pancreatic adenocarcinoma (PDAC), according to long-term follow-up results of a phase 1/2 study presented at the European Society of Medical Oncology (ESMO) Virtual World Congress on Gastrointestinal Cancer 2020.1

Although, the combination of 5-FU, LV plus oxaliplatin, and non-liposomal irinotecan (FOLFIRINOX), as well as gemcitabine plus nab-paclitaxel, are established first-line treatment regimens for patients with metastatic PDA, irinotecan has a short half-life and is associated with dose-limiting toxicity.

In contrast, preclinical studies of liposomal irinotecan have shown longer persistence of its active metabolite compared with non-liposomal irinotecan. This agent is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic PDAC that has progressed following treatment with a gemcitabine-based regimen.2

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The dose-escalation, safety run-in portion of this study ( Identifier: NCT02551991) evaluated the safety and tolerability of NALIRIFOX in treatment-naïve patients with advanced/metastatic PDA using a traditional 3 + 3 design. Based on these results, the dose-expansion portion of the study involved administration of liposomal irinotecan, 5-FU, LV, and oxaliplatin at doses of 50, 2400, 40, and 60 mg/m2, respectively.

In addition to the primary study end points of safety, tolerability, and determination of the recommended drug doses for future development, secondary study endpoints included determination of best overall response by RECIST 1.1 criteria, as well as progression-free survival (PFS), overall survival (OS), and duration of response (DoR).

For the pooled population of 32 patients treated with NALIRIFOX at the specified component drug doses, the median patient age was 58 years, and stage IV disease was present in 87.5%.

Regarding safety, grade 3 or higher treatment-related adverse events (AEs) were reported in 68.8% of patients, including neutropenia and febrile neutropenia in 31.3% and 12.5% of patients, respectively.

In addition, 3 patients (9.4%) experienced a serious AE leading to death.

The median PFS and OS were 9.2 months and 12.6 months, respectively, with an overall response rate of 34.4%, disease-control rate of 71.9%, and a median DoR of 9.4 months.

Based on these results, liposomal irinotecan administered as NALIRIFOX for the treatment of metastatic PDAC was granted Fast Track status by the FDA in June 2020.3 Specifically, NALIRIFOX is currently being compared with gemcitabine plus nab-paclitaxelin in adults with previously untreated metastatic PDAC in the randomized NAPOLI-3 clinical trial ( Identifier: NCT04083235).

Disclosures: Funding for this research was provided by Ipsen Biopharmaceuticals, Inc.


  1. Wainberg, ZA, Bekaii-Saab T, Boland PM, et al. First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: long-term follow-up results from a phase 1/2 study. Presented at: the ESMO Virtual World Congress on Gastrointestinal Cancer; July 1-4, 2020. Abstract LBA 1.
  2. Liposomal irinotecan (Onivyde) [package insert]. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc.; 2017.
  3. Ipsen. Ipsen receives FDA Fast Track designation for liposomal irinotecan (Onivyde®) as a first-line combination treatment for metastatic pancreatic cancer [press release]. Published June 17, 2020. Accessed July 8, 2020.